Author: Steven M Schwarz, Professor of Pediatrics, Children's Hospital at Downstate, SUNY-Downstate Medical Center
Coauthor(s): Michael Freemark, MD, Professor of Pediatrics, Duke University;
http://emedicine.medscape.com/article/985333-overview
Updated: Apr 13, 2010
Background
Obesity is the most prevalent nutritional disorder among children and adolescents in the United States. Currently available data report that approximately 21-24% of American children and adolescents are overweight and that another 16-18% are obese; the prevalence of obesity is highest among specific ethnic groups.
Childhood obesity predisposes to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and renal disease, and reproductive dysfunction. It also increases the risk of adult-onset obesity and cardiovascular disease.
Operational definitions of obesity in adults are derived from statistical data analyzing the association between body mass and the risk of acute and long-term morbidity and mortality. Because acute medical complications of obesity are less common in children and adolescents than in adults, and because longitudinal data on the relation between childhood weight and adult morbidity and mortality are more difficult to interpret, no single definition of obesity in childhood and adolescence has gained universal approval.
Some investigators have used the terms overweight, obese, and morbidly obese to refer to children and adolescents whose weights exceed those expected for heights by 20%, 50%, and 80-100%, respectively.
The body mass index (BMI) has not been consistently used or validated in children younger than 2 years. Because weight varies in a continuous rather than a stepwise fashion, the use of these arbitrary criteria is problematic and may be misleading. Nevertheless, children and adolescents defined as overweight or obese according to published criteria are highly likely to maintain this ponderal status as adults.
The BMI is a continuous, although imperfect, measure of body fatness. Calculated as weight (kg) divided by height (m2), BMI corrects for body size and can be readily and reliably quantified in clinical settings.
The BMI correlates closely with total body fat (TBF), which is estimated using dual-energy x-ray absorptiometry (DEXA) scanning in children who are overweight and obese.
Normal values for BMI vary with age, sex, and pubertal status, and standard curves representing the 5th through the 95th percentiles for BMI in childhood and adolescence have been generated using data from the National Health and Nutrition Examination Surveys of 1988-1994.1
Consensus committees have recommended that children and adolescents be considered overweight or obese if the BMI exceeds the 85th or 95th percentiles, on curves generated from the 1963-1965 and 1966-1970 surveys, or exceeds 30 kg/m2 at any age.2
McGavock et al demonstrated that low cardiorespiratory fitness and reductions in fitness over time are significantly associated with weight gain and the risk of being overweight in children aged 6-15 years. Analysis on a cohort of 902 schoolchildren showed higher waist circumference and disproportionate weight gain over a 12-month follow-up period in those children with low cardiorespiratory fitness (P < 0.05). The 12-month risk of overweight classification was 3.5-fold (95% confidence interval [CI], 2.0-6.0; P < 0.001) higher in youth with low cardiorespiratory fitness, relative to fit peers. Reductions in cardiorespiratory fitness were significantly and independently associated with increasing body mass index (P < 0.05).
Pathophysiology
During childhood and adolescence, excess fat accumulates when total energy intake exceeds total energy expenditure. This energy imbalance can result from excessive energy intake and/or reduced energy expenditure, the latter is usually a consequence of a sedentary lifestyle. This is particularly associated with excessive television viewing, excessive computer use, and insufficient physical activity. In infancy, excess fat deposition occurs when excess energy is provided, especially when protein-to-energy ratio is altered. This is often seen when feedings are supplemented with additives such as carbohydrates or fat and protein content remains the same.
In individuals who are obese, dysfunction in the gut-brain-hypothalamic axis via the ghrelin/leptin hormonal pathway has been suggested to have a role in abnormal appetite control and excess energy intake. See the image below.
Studies indicate that dysfunction in this hormonal axis may be the causative factor in as many as 10% of obese subjects, with emphasis particularly on those individuals who appear to manifest familial morbid obesity. In these families, several reports have shown a dramatic, weight loss response to hormone replacement therapy in patients with leptin deficiency. Reductions in energy expenditure characterize other hormonal deficiency states, including hypothyroidism and growth hormone deficiency. Increases in energy intake are observed in genetic syndromes, such as Prader-Willi syndrome, Cushing syndrome, and drug-induced obesity.
Despite observations of an etiologic role for genetic and hormonal disorders, these factors alone do not explain the excess weight gain observed in most patients who have obesity and are referred to physicians for evaluation and treatment.
Although most overweight children have a familial form of obesity, with 1 or 2 obese parents, excess weight gain in obese children clearly depends on both genetic and environmental factors.
Correlations between parent and child habitus likely reflect, at least in part, the familial patterns of food intake, exercise, and selection of leisure activity (including amount of television watching), as well as familial and cultural patterns of food selection.
Nevertheless, evidence from twin, adoption, and family studies suggests that genetic factors also play a considerable role in the development of childhood obesity.
Concordance rates for obesity and type 2 diabetes mellitus are higher in monozygotic twins than in dizygotic twins, and measures of TBF correlate nearly as strongly in monozygotic twins reared apart (r = 0.61) as in monozygotic twins reared together (r = 0.75). Still, genetic factors cannot explain the increased prevalence of obesity observed among American adolescents over the past generation.
The accumulation of body fat, particularly in a visceral distribution, reduces the sensitivity to insulin in skeletal muscle, liver tissue, and adipose tissue; this "insulin resistance" predisposes to glucose intolerance and hypertriglyceridemia. Low levels of high-density lipoprotein (HDL), observed both genetically and in association with a sedentary lifestyle, likely contribute to the increase of premature coronary artery disease observed in adults with obesity. Increases in circulating levels of insulin and insulin-like growth factor I may increase blood pressure (BP) and may stimulate the production of androgens from ovarian and adrenocortical cells, with consequent dysmenorrhea and virilization in females. Aromatization of adrenal androgens to estrone leads to gynecomastia in males. The insulin resistance, dyslipidemia, and hypertension predispose to type 2 diabetes and cardiovascular disease, reducing life expectancy.
Frequency
United States
Using BMI criteria, the most recent national surveys demonstrate that 21-24% of American children and adolescents are overweight and that another 16-18% are obese. These findings indicate that the prevalence of overweight (BMI = ³ 85th percentile) children and adolescents in the United States has increased by 50-60% in a single generation, and the prevalence of obesity has doubled. The prevalence of obesity in American Indians, Hawaiians, Hispanics, and blacks is 10-40% higher than in whites.
Mortality/Morbidity
For many years, complications arising from obesity were considered unusual in childhood. However, a plethora of minor and major problems may arise in children and adolescents with obesity; most of these problems have considerable impact on quality of life, and some may reduce life expectancy.
Acute complications
o Acute complications of childhood obesity include type 2 diabetes, hypertension, hyperlipidemia, accelerated growth and bone maturation, ovarian hyperandrogenism and gynecomastia, cholecystitis, pancreatitis, and pseudotumor cerebri. Fatty liver is common; rarely, patients develop cirrhosis and renal disease (focal glomerulosclerosis). Sleep apnea and sleep-disordered breathing are common in children and adolescents with obesity; in some cases, the apnea is accompanied by neurocognitive dysfunction. Tonsillectomy and adenoidectomy and/or bilevel positive airway pressure/continuous positive airway pressure (BIPAP/CPAP) may be beneficial in patients with reduced oxygenation or carbon dioxide retention.
o Numerous orthopedic disorders, including genu valgum, slipped capital femoral epiphysis, and tibia vara, are observed more commonly in children with obesity. Excess weight in young children can cause bowing of the tibia and femurs; the resulting overgrowth of the proximal tibial metaphysis is called Blount disease.
o Evidence of liver dysfunction, with elevated plasma concentrations of transaminases, is observed in 20% of children with obesity; the liver dysfunction most commonly reflects hepatic steatosis, but cirrhosis may develop in rare instances. Vitamin E supplements may be effective in reversing this so-called steatohepatitis, suggesting that the disorder reflects a relative state of vitamin E deficiency.4 Cholelithiasis is more common in adults with obesity than in adults with normal weight. Although gallstones are unusual in childhood, nearly one half of all cases of cholecystitis in adolescents are associated with obesity. Cholecystitis may be even more common during rapid weight loss, particularly with very controlled–energy diets.
o Emotional and psychosocial sequelae are widespread. Anecdotal evidence suggests that depression and eating disorders are common in children and adolescents referred to obesity clinics. Prejudice and discrimination against individuals with obesity are ubiquitous within US culture; even young children have been found to regard their peers who have obesity in negative ways. Social isolation, peer problems, and lower self-esteem are frequently observed.
o Obesity during childhood and adolescence is associated with numerous cardiovascular risk factors, including hyperinsulinism and insulin resistance, hypercholesterolemia, hypertriglyceridemia, reduced levels of HDL, and hypertension. A hallmark of insulin resistance is acanthosis nigricans, the presence of which indicates an increased risk of type 2 diabetes. Adolescent girls with obesity also demonstrate a hyperandrogenic profile, consisting of elevated serum concentrations of androstenedione, dehydroepiandrosterone-sulfate (DHEA-S), and testosterone, as well as reduced levels of sex hormone–binding globulin. The clinical picture resembles that of polycystic ovary syndrome (PCOS). The excess androgens are of adrenal and ovarian origin and may be related, at least in part, to increased serum concentrations of insulin and insulin growth factor 1 (IGF-I).
o Among sexually mature adolescents, changes in serum lipids and androgens seem to correlate more strongly with body fat distribution than with absolute weight. Thus, adolescents with central obesity (ie, android or abdominal fat pattern) are more likely to manifest these cardiovascular risk factors than individuals with peripheral obesity (ie, gynoid or gluteal pattern). In prepubertal children, however, the cardiovascular risk factors correlate better with body weight than with body fat distribution. The increasing prevalence of obesity in childhood and adolescence, accompanied by insulin resistance, appears to explain the increasing incidence of type 2 diabetes in adolescents, particularly in minority populations.
* Long-term complications
o Obesity during childhood and adolescence is associated with an increased risk of obesity during adulthood, with its attendant long-term health risks. This increased risk appears most pronounced for adolescent males with moderate-to-severe obesity. The long-term implications of obesity during infancy and early childhood on subsequent health are less clear. In general, the proportion of children with obesity who have obesity as adults increases with increased age at onset of obesity, such that 26-41% of preschoolers with obesity have obesity as adults, compared with 42-63% of school-aged children. Additionally, the higher the degree of obesity during childhood, the higher the risk of adult obesity. Individuals aged 18 years individuals with a BMI at or above the 95th percentile have a 66-78% risk of being overweight at age 35 years.
o The dramatic increase in the prevalence of type 2 diabetes among adolescents with obesity is likely to be accompanied by a host of diabetic-related complications in adulthood and a reduction in life span. The epidemiological data, although limited, indicate that adolescent obesity is associated with increased morbidity and mortality in later life.
o An increased risk of death from all causes and from coronary artery disease (CAD) has been consistently observed in males, but not in females, who had obesity during adolescence. In a follow-up of the Harvard Growth Study, the risk of morbidity from CAD and atherosclerosis was increased among men and women who had been overweight (BMI >75th percentile) as teenagers. Gout and colorectal cancer increased among men who had obesity as adolescents, and arthritis increased among women who had obesity as adolescents. Many of these adverse health outcomes appear to be independent of adult weight, suggesting a direct effect of adolescent obesity on adult health and mortality.
o Psychosocial dysfunction in individuals who have obesity in childhood and adolescence is a serious concern. Among teens and young adults who were tracked after 7 years, overweight females were found to have completed less schooling, were less likely to have married, and had higher rates of household poverty compared to their nonoverweight peers. For overweight males, the only adverse outcome was a decreased likelihood of being married.
Thursday, July 29, 2010
Obesity in Children
Author: Steven M Schwarz, Professor of Pediatrics, Children's Hospital at Downstate, SUNY-Downstate Medical Center
Coauthor(s): Michael Freemark, MD, Professor of Pediatrics, Duke University;
http://emedicine.medscape.com/article/985333-overview
Updated: Apr 13, 2010
Background
Obesity is the most prevalent nutritional disorder among children and adolescents in the United States. Currently available data report that approximately 21-24% of American children and adolescents are overweight and that another 16-18% are obese; the prevalence of obesity is highest among specific ethnic groups.
Childhood obesity predisposes to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and renal disease, and reproductive dysfunction. It also increases the risk of adult-onset obesity and cardiovascular disease.
Operational definitions of obesity in adults are derived from statistical data analyzing the association between body mass and the risk of acute and long-term morbidity and mortality. Because acute medical complications of obesity are less common in children and adolescents than in adults, and because longitudinal data on the relation between childhood weight and adult morbidity and mortality are more difficult to interpret, no single definition of obesity in childhood and adolescence has gained universal approval.
Some investigators have used the terms overweight, obese, and morbidly obese to refer to children and adolescents whose weights exceed those expected for heights by 20%, 50%, and 80-100%, respectively.
The body mass index (BMI) has not been consistently used or validated in children younger than 2 years. Because weight varies in a continuous rather than a stepwise fashion, the use of these arbitrary criteria is problematic and may be misleading. Nevertheless, children and adolescents defined as overweight or obese according to published criteria are highly likely to maintain this ponderal status as adults.
The BMI is a continuous, although imperfect, measure of body fatness. Calculated as weight (kg) divided by height (m2), BMI corrects for body size and can be readily and reliably quantified in clinical settings.
The BMI correlates closely with total body fat (TBF), which is estimated using dual-energy x-ray absorptiometry (DEXA) scanning in children who are overweight and obese.
Normal values for BMI vary with age, sex, and pubertal status, and standard curves representing the 5th through the 95th percentiles for BMI in childhood and adolescence have been generated using data from the National Health and Nutrition Examination Surveys of 1988-1994.1
Consensus committees have recommended that children and adolescents be considered overweight or obese if the BMI exceeds the 85th or 95th percentiles, on curves generated from the 1963-1965 and 1966-1970 surveys, or exceeds 30 kg/m2 at any age.2
McGavock et al demonstrated that low cardiorespiratory fitness and reductions in fitness over time are significantly associated with weight gain and the risk of being overweight in children aged 6-15 years. Analysis on a cohort of 902 schoolchildren showed higher waist circumference and disproportionate weight gain over a 12-month follow-up period in those children with low cardiorespiratory fitness (P < 0.05). The 12-month risk of overweight classification was 3.5-fold (95% confidence interval [CI], 2.0-6.0; P < 0.001) higher in youth with low cardiorespiratory fitness, relative to fit peers. Reductions in cardiorespiratory fitness were significantly and independently associated with increasing body mass index (P < 0.05). Pathophysiology During childhood and adolescence, excess fat accumulates when total energy intake exceeds total energy expenditure. This energy imbalance can result from excessive energy intake and/or reduced energy expenditure, the latter is usually a consequence of a sedentary lifestyle. This is particularly associated with excessive television viewing, excessive computer use, and insufficient physical activity. In infancy, excess fat deposition occurs when excess energy is provided, especially when protein-to-energy ratio is altered. This is often seen when feedings are supplemented with additives such as carbohydrates or fat and protein content remains the same. In individuals who are obese, dysfunction in the gut-brain-hypothalamic axis via the ghrelin/leptin hormonal pathway has been suggested to have a role in abnormal appetite control and excess energy intake. See the image below. Studies indicate that dysfunction in this hormonal axis may be the causative factor in as many as 10% of obese subjects, with emphasis particularly on those individuals who appear to manifest familial morbid obesity. In these families, several reports have shown a dramatic, weight loss response to hormone replacement therapy in patients with leptin deficiency. Reductions in energy expenditure characterize other hormonal deficiency states, including hypothyroidism and growth hormone deficiency. Increases in energy intake are observed in genetic syndromes, such as Prader-Willi syndrome, Cushing syndrome, and drug-induced obesity. Despite observations of an etiologic role for genetic and hormonal disorders, these factors alone do not explain the excess weight gain observed in most patients who have obesity and are referred to physicians for evaluation and treatment. Although most overweight children have a familial form of obesity, with 1 or 2 obese parents, excess weight gain in obese children clearly depends on both genetic and environmental factors. Correlations between parent and child habitus likely reflect, at least in part, the familial patterns of food intake, exercise, and selection of leisure activity (including amount of television watching), as well as familial and cultural patterns of food selection. Nevertheless, evidence from twin, adoption, and family studies suggests that genetic factors also play a considerable role in the development of childhood obesity. Concordance rates for obesity and type 2 diabetes mellitus are higher in monozygotic twins than in dizygotic twins, and measures of TBF correlate nearly as strongly in monozygotic twins reared apart (r = 0.61) as in monozygotic twins reared together (r = 0.75). Still, genetic factors cannot explain the increased prevalence of obesity observed among American adolescents over the past generation. The accumulation of body fat, particularly in a visceral distribution, reduces the sensitivity to insulin in skeletal muscle, liver tissue, and adipose tissue; this "insulin resistance" predisposes to glucose intolerance and hypertriglyceridemia. Low levels of high-density lipoprotein (HDL), observed both genetically and in association with a sedentary lifestyle, likely contribute to the increase of premature coronary artery disease observed in adults with obesity. Increases in circulating levels of insulin and insulin-like growth factor I may increase blood pressure (BP) and may stimulate the production of androgens from ovarian and adrenocortical cells, with consequent dysmenorrhea and virilization in females. Aromatization of adrenal androgens to estrone leads to gynecomastia in males. The insulin resistance, dyslipidemia, and hypertension predispose to type 2 diabetes and cardiovascular disease, reducing life expectancy. Frequency United States Using BMI criteria, the most recent national surveys demonstrate that 21-24% of American children and adolescents are overweight and that another 16-18% are obese. These findings indicate that the prevalence of overweight (BMI = ³ 85th percentile) children and adolescents in the United States has increased by 50-60% in a single generation, and the prevalence of obesity has doubled. The prevalence of obesity in American Indians, Hawaiians, Hispanics, and blacks is 10-40% higher than in whites. Mortality/Morbidity For many years, complications arising from obesity were considered unusual in childhood. However, a plethora of minor and major problems may arise in children and adolescents with obesity; most of these problems have considerable impact on quality of life, and some may reduce life expectancy. Acute complications o Acute complications of childhood obesity include type 2 diabetes, hypertension, hyperlipidemia, accelerated growth and bone maturation, ovarian hyperandrogenism and gynecomastia, cholecystitis, pancreatitis, and pseudotumor cerebri. Fatty liver is common; rarely, patients develop cirrhosis and renal disease (focal glomerulosclerosis). Sleep apnea and sleep-disordered breathing are common in children and adolescents with obesity; in some cases, the apnea is accompanied by neurocognitive dysfunction. Tonsillectomy and adenoidectomy and/or bilevel positive airway pressure/continuous positive airway pressure (BIPAP/CPAP) may be beneficial in patients with reduced oxygenation or carbon dioxide retention. o Numerous orthopedic disorders, including genu valgum, slipped capital femoral epiphysis, and tibia vara, are observed more commonly in children with obesity. Excess weight in young children can cause bowing of the tibia and femurs; the resulting overgrowth of the proximal tibial metaphysis is called Blount disease. o Evidence of liver dysfunction, with elevated plasma concentrations of transaminases, is observed in 20% of children with obesity; the liver dysfunction most commonly reflects hepatic steatosis, but cirrhosis may develop in rare instances. Vitamin E supplements may be effective in reversing this so-called steatohepatitis, suggesting that the disorder reflects a relative state of vitamin E deficiency.4 Cholelithiasis is more common in adults with obesity than in adults with normal weight. Although gallstones are unusual in childhood, nearly one half of all cases of cholecystitis in adolescents are associated with obesity. Cholecystitis may be even more common during rapid weight loss, particularly with very controlled–energy diets. o Emotional and psychosocial sequelae are widespread. Anecdotal evidence suggests that depression and eating disorders are common in children and adolescents referred to obesity clinics. Prejudice and discrimination against individuals with obesity are ubiquitous within US culture; even young children have been found to regard their peers who have obesity in negative ways. Social isolation, peer problems, and lower self-esteem are frequently observed. o Obesity during childhood and adolescence is associated with numerous cardiovascular risk factors, including hyperinsulinism and insulin resistance, hypercholesterolemia, hypertriglyceridemia, reduced levels of HDL, and hypertension. A hallmark of insulin resistance is acanthosis nigricans, the presence of which indicates an increased risk of type 2 diabetes. Adolescent girls with obesity also demonstrate a hyperandrogenic profile, consisting of elevated serum concentrations of androstenedione, dehydroepiandrosterone-sulfate (DHEA-S), and testosterone, as well as reduced levels of sex hormone–binding globulin. The clinical picture resembles that of polycystic ovary syndrome (PCOS). The excess androgens are of adrenal and ovarian origin and may be related, at least in part, to increased serum concentrations of insulin and insulin growth factor 1 (IGF-I). o Among sexually mature adolescents, changes in serum lipids and androgens seem to correlate more strongly with body fat distribution than with absolute weight. Thus, adolescents with central obesity (ie, android or abdominal fat pattern) are more likely to manifest these cardiovascular risk factors than individuals with peripheral obesity (ie, gynoid or gluteal pattern). In prepubertal children, however, the cardiovascular risk factors correlate better with body weight than with body fat distribution. The increasing prevalence of obesity in childhood and adolescence, accompanied by insulin resistance, appears to explain the increasing incidence of type 2 diabetes in adolescents, particularly in minority populations. * Long-term complications o Obesity during childhood and adolescence is associated with an increased risk of obesity during adulthood, with its attendant long-term health risks. This increased risk appears most pronounced for adolescent males with moderate-to-severe obesity. The long-term implications of obesity during infancy and early childhood on subsequent health are less clear. In general, the proportion of children with obesity who have obesity as adults increases with increased age at onset of obesity, such that 26-41% of preschoolers with obesity have obesity as adults, compared with 42-63% of school-aged children. Additionally, the higher the degree of obesity during childhood, the higher the risk of adult obesity. Individuals aged 18 years individuals with a BMI at or above the 95th percentile have a 66-78% risk of being overweight at age 35 years. o The dramatic increase in the prevalence of type 2 diabetes among adolescents with obesity is likely to be accompanied by a host of diabetic-related complications in adulthood and a reduction in life span. The epidemiological data, although limited, indicate that adolescent obesity is associated with increased morbidity and mortality in later life. o An increased risk of death from all causes and from coronary artery disease (CAD) has been consistently observed in males, but not in females, who had obesity during adolescence. In a follow-up of the Harvard Growth Study, the risk of morbidity from CAD and atherosclerosis was increased among men and women who had been overweight (BMI >75th percentile) as teenagers. Gout and colorectal cancer increased among men who had obesity as adolescents, and arthritis increased among women who had obesity as adolescents. Many of these adverse health outcomes appear to be independent of adult weight, suggesting a direct effect of adolescent obesity on adult health and mortality.
o Psychosocial dysfunction in individuals who have obesity in childhood and adolescence is a serious concern. Among teens and young adults who were tracked after 7 years, overweight females were found to have completed less schooling, were less likely to have married, and had higher rates of household poverty compared to their nonoverweight peers. For overweight males, the only adverse outcome was a decreased likelihood of being married.
Coauthor(s): Michael Freemark, MD, Professor of Pediatrics, Duke University;
http://emedicine.medscape.com/article/985333-overview
Updated: Apr 13, 2010
Background
Obesity is the most prevalent nutritional disorder among children and adolescents in the United States. Currently available data report that approximately 21-24% of American children and adolescents are overweight and that another 16-18% are obese; the prevalence of obesity is highest among specific ethnic groups.
Childhood obesity predisposes to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and renal disease, and reproductive dysfunction. It also increases the risk of adult-onset obesity and cardiovascular disease.
Operational definitions of obesity in adults are derived from statistical data analyzing the association between body mass and the risk of acute and long-term morbidity and mortality. Because acute medical complications of obesity are less common in children and adolescents than in adults, and because longitudinal data on the relation between childhood weight and adult morbidity and mortality are more difficult to interpret, no single definition of obesity in childhood and adolescence has gained universal approval.
Some investigators have used the terms overweight, obese, and morbidly obese to refer to children and adolescents whose weights exceed those expected for heights by 20%, 50%, and 80-100%, respectively.
The body mass index (BMI) has not been consistently used or validated in children younger than 2 years. Because weight varies in a continuous rather than a stepwise fashion, the use of these arbitrary criteria is problematic and may be misleading. Nevertheless, children and adolescents defined as overweight or obese according to published criteria are highly likely to maintain this ponderal status as adults.
The BMI is a continuous, although imperfect, measure of body fatness. Calculated as weight (kg) divided by height (m2), BMI corrects for body size and can be readily and reliably quantified in clinical settings.
The BMI correlates closely with total body fat (TBF), which is estimated using dual-energy x-ray absorptiometry (DEXA) scanning in children who are overweight and obese.
Normal values for BMI vary with age, sex, and pubertal status, and standard curves representing the 5th through the 95th percentiles for BMI in childhood and adolescence have been generated using data from the National Health and Nutrition Examination Surveys of 1988-1994.1
Consensus committees have recommended that children and adolescents be considered overweight or obese if the BMI exceeds the 85th or 95th percentiles, on curves generated from the 1963-1965 and 1966-1970 surveys, or exceeds 30 kg/m2 at any age.2
McGavock et al demonstrated that low cardiorespiratory fitness and reductions in fitness over time are significantly associated with weight gain and the risk of being overweight in children aged 6-15 years. Analysis on a cohort of 902 schoolchildren showed higher waist circumference and disproportionate weight gain over a 12-month follow-up period in those children with low cardiorespiratory fitness (P < 0.05). The 12-month risk of overweight classification was 3.5-fold (95% confidence interval [CI], 2.0-6.0; P < 0.001) higher in youth with low cardiorespiratory fitness, relative to fit peers. Reductions in cardiorespiratory fitness were significantly and independently associated with increasing body mass index (P < 0.05). Pathophysiology During childhood and adolescence, excess fat accumulates when total energy intake exceeds total energy expenditure. This energy imbalance can result from excessive energy intake and/or reduced energy expenditure, the latter is usually a consequence of a sedentary lifestyle. This is particularly associated with excessive television viewing, excessive computer use, and insufficient physical activity. In infancy, excess fat deposition occurs when excess energy is provided, especially when protein-to-energy ratio is altered. This is often seen when feedings are supplemented with additives such as carbohydrates or fat and protein content remains the same. In individuals who are obese, dysfunction in the gut-brain-hypothalamic axis via the ghrelin/leptin hormonal pathway has been suggested to have a role in abnormal appetite control and excess energy intake. See the image below. Studies indicate that dysfunction in this hormonal axis may be the causative factor in as many as 10% of obese subjects, with emphasis particularly on those individuals who appear to manifest familial morbid obesity. In these families, several reports have shown a dramatic, weight loss response to hormone replacement therapy in patients with leptin deficiency. Reductions in energy expenditure characterize other hormonal deficiency states, including hypothyroidism and growth hormone deficiency. Increases in energy intake are observed in genetic syndromes, such as Prader-Willi syndrome, Cushing syndrome, and drug-induced obesity. Despite observations of an etiologic role for genetic and hormonal disorders, these factors alone do not explain the excess weight gain observed in most patients who have obesity and are referred to physicians for evaluation and treatment. Although most overweight children have a familial form of obesity, with 1 or 2 obese parents, excess weight gain in obese children clearly depends on both genetic and environmental factors. Correlations between parent and child habitus likely reflect, at least in part, the familial patterns of food intake, exercise, and selection of leisure activity (including amount of television watching), as well as familial and cultural patterns of food selection. Nevertheless, evidence from twin, adoption, and family studies suggests that genetic factors also play a considerable role in the development of childhood obesity. Concordance rates for obesity and type 2 diabetes mellitus are higher in monozygotic twins than in dizygotic twins, and measures of TBF correlate nearly as strongly in monozygotic twins reared apart (r = 0.61) as in monozygotic twins reared together (r = 0.75). Still, genetic factors cannot explain the increased prevalence of obesity observed among American adolescents over the past generation. The accumulation of body fat, particularly in a visceral distribution, reduces the sensitivity to insulin in skeletal muscle, liver tissue, and adipose tissue; this "insulin resistance" predisposes to glucose intolerance and hypertriglyceridemia. Low levels of high-density lipoprotein (HDL), observed both genetically and in association with a sedentary lifestyle, likely contribute to the increase of premature coronary artery disease observed in adults with obesity. Increases in circulating levels of insulin and insulin-like growth factor I may increase blood pressure (BP) and may stimulate the production of androgens from ovarian and adrenocortical cells, with consequent dysmenorrhea and virilization in females. Aromatization of adrenal androgens to estrone leads to gynecomastia in males. The insulin resistance, dyslipidemia, and hypertension predispose to type 2 diabetes and cardiovascular disease, reducing life expectancy. Frequency United States Using BMI criteria, the most recent national surveys demonstrate that 21-24% of American children and adolescents are overweight and that another 16-18% are obese. These findings indicate that the prevalence of overweight (BMI = ³ 85th percentile) children and adolescents in the United States has increased by 50-60% in a single generation, and the prevalence of obesity has doubled. The prevalence of obesity in American Indians, Hawaiians, Hispanics, and blacks is 10-40% higher than in whites. Mortality/Morbidity For many years, complications arising from obesity were considered unusual in childhood. However, a plethora of minor and major problems may arise in children and adolescents with obesity; most of these problems have considerable impact on quality of life, and some may reduce life expectancy. Acute complications o Acute complications of childhood obesity include type 2 diabetes, hypertension, hyperlipidemia, accelerated growth and bone maturation, ovarian hyperandrogenism and gynecomastia, cholecystitis, pancreatitis, and pseudotumor cerebri. Fatty liver is common; rarely, patients develop cirrhosis and renal disease (focal glomerulosclerosis). Sleep apnea and sleep-disordered breathing are common in children and adolescents with obesity; in some cases, the apnea is accompanied by neurocognitive dysfunction. Tonsillectomy and adenoidectomy and/or bilevel positive airway pressure/continuous positive airway pressure (BIPAP/CPAP) may be beneficial in patients with reduced oxygenation or carbon dioxide retention. o Numerous orthopedic disorders, including genu valgum, slipped capital femoral epiphysis, and tibia vara, are observed more commonly in children with obesity. Excess weight in young children can cause bowing of the tibia and femurs; the resulting overgrowth of the proximal tibial metaphysis is called Blount disease. o Evidence of liver dysfunction, with elevated plasma concentrations of transaminases, is observed in 20% of children with obesity; the liver dysfunction most commonly reflects hepatic steatosis, but cirrhosis may develop in rare instances. Vitamin E supplements may be effective in reversing this so-called steatohepatitis, suggesting that the disorder reflects a relative state of vitamin E deficiency.4 Cholelithiasis is more common in adults with obesity than in adults with normal weight. Although gallstones are unusual in childhood, nearly one half of all cases of cholecystitis in adolescents are associated with obesity. Cholecystitis may be even more common during rapid weight loss, particularly with very controlled–energy diets. o Emotional and psychosocial sequelae are widespread. Anecdotal evidence suggests that depression and eating disorders are common in children and adolescents referred to obesity clinics. Prejudice and discrimination against individuals with obesity are ubiquitous within US culture; even young children have been found to regard their peers who have obesity in negative ways. Social isolation, peer problems, and lower self-esteem are frequently observed. o Obesity during childhood and adolescence is associated with numerous cardiovascular risk factors, including hyperinsulinism and insulin resistance, hypercholesterolemia, hypertriglyceridemia, reduced levels of HDL, and hypertension. A hallmark of insulin resistance is acanthosis nigricans, the presence of which indicates an increased risk of type 2 diabetes. Adolescent girls with obesity also demonstrate a hyperandrogenic profile, consisting of elevated serum concentrations of androstenedione, dehydroepiandrosterone-sulfate (DHEA-S), and testosterone, as well as reduced levels of sex hormone–binding globulin. The clinical picture resembles that of polycystic ovary syndrome (PCOS). The excess androgens are of adrenal and ovarian origin and may be related, at least in part, to increased serum concentrations of insulin and insulin growth factor 1 (IGF-I). o Among sexually mature adolescents, changes in serum lipids and androgens seem to correlate more strongly with body fat distribution than with absolute weight. Thus, adolescents with central obesity (ie, android or abdominal fat pattern) are more likely to manifest these cardiovascular risk factors than individuals with peripheral obesity (ie, gynoid or gluteal pattern). In prepubertal children, however, the cardiovascular risk factors correlate better with body weight than with body fat distribution. The increasing prevalence of obesity in childhood and adolescence, accompanied by insulin resistance, appears to explain the increasing incidence of type 2 diabetes in adolescents, particularly in minority populations. * Long-term complications o Obesity during childhood and adolescence is associated with an increased risk of obesity during adulthood, with its attendant long-term health risks. This increased risk appears most pronounced for adolescent males with moderate-to-severe obesity. The long-term implications of obesity during infancy and early childhood on subsequent health are less clear. In general, the proportion of children with obesity who have obesity as adults increases with increased age at onset of obesity, such that 26-41% of preschoolers with obesity have obesity as adults, compared with 42-63% of school-aged children. Additionally, the higher the degree of obesity during childhood, the higher the risk of adult obesity. Individuals aged 18 years individuals with a BMI at or above the 95th percentile have a 66-78% risk of being overweight at age 35 years. o The dramatic increase in the prevalence of type 2 diabetes among adolescents with obesity is likely to be accompanied by a host of diabetic-related complications in adulthood and a reduction in life span. The epidemiological data, although limited, indicate that adolescent obesity is associated with increased morbidity and mortality in later life. o An increased risk of death from all causes and from coronary artery disease (CAD) has been consistently observed in males, but not in females, who had obesity during adolescence. In a follow-up of the Harvard Growth Study, the risk of morbidity from CAD and atherosclerosis was increased among men and women who had been overweight (BMI >75th percentile) as teenagers. Gout and colorectal cancer increased among men who had obesity as adolescents, and arthritis increased among women who had obesity as adolescents. Many of these adverse health outcomes appear to be independent of adult weight, suggesting a direct effect of adolescent obesity on adult health and mortality.
o Psychosocial dysfunction in individuals who have obesity in childhood and adolescence is a serious concern. Among teens and young adults who were tracked after 7 years, overweight females were found to have completed less schooling, were less likely to have married, and had higher rates of household poverty compared to their nonoverweight peers. For overweight males, the only adverse outcome was a decreased likelihood of being married.
Tuesday, July 27, 2010
Treatment of Children With Head Lice in the School Setting Reviewed
From Medscape Medical News
Laurie Barclay, MD
July 26, 2010 — Current diagnosis, treatment protocols, and management guidelines regarding children with head lice in the school setting are presented in a clinical report posted online July 26 and in the August print issue of Pediatrics.
"Head lice infestation is associated with limited morbidity but causes a high level of anxiety among parents of school-aged children," write Barbara L. Frankowski, MD, MPH, and Joseph A. Bocchini Jr, MD, from the Council on School Health and Committee on Infectious Diseases, 2006-2010. "Since the 2002 clinical report on head lice was published by the American Academy of Pediatrics, patterns of resistance to products available over-the-counter and by prescription have changed, and additional mechanical means of removing head lice have been explored. This revised clinical report clarifies current diagnosis and treatment protocols and provides guidance for the management of children with head lice in the school setting."
The reference standard for diagnosing head lice is finding a live louse on the head, although infestation can also be diagnosed by using a louse comb or by observation of eggs at the nape of the neck or behind the ears, within 1 cm of the scalp.
Despite the impossibility of preventing all head lice infestations, children should be taught not to share personal items such as combs, brushes, and hats.
"Never initiate treatment unless there is a clear diagnosis of head lice," the review authors write. "The ideal treatment for lice would be completely safe, free of harmful chemicals, readily available without a prescription, easy to use, and inexpensive. When recommending a treatment, paediatricians should take into account effectiveness and safety, local patterns of resistance (if known), ease of use, and cost."
Specific Recommendations
Specific recommendations regarding current diagnosis, management, and treatment protocols for children with head lice in the school setting include the following:
* Head lice should not be a reason for an otherwise healthy child to be excluded from or kept absent from school. No-nit policies for return to school should therefore no longer be enforced.
* Pediatricians should know how to manage and treat head lice infestations so that they can actively inform families, schools, and other community agencies.
* For treatment of active infestations, 1% permethrin or pyrethrins are recommended unless resistance to these medications has been proven in the community.
* School staff and parents should be given detailed instructions on the proper use of recommended treatments. Current permethrin or pyrethrin products are not completely ovicidal, necessitating that they be applied at least twice at proper intervals. This is also recommended if live lice persist after treatment with malathion. To prevent spread, manual removal of nits is not necessary immediately after pediculicide therapy. However, nit removal may be considered in the school setting to reduce diagnostic confusion.
* Feasible alternatives to use of pediculicide may include "wet-combing" or an occlusive method, such as petroleum jelly or a mild skin cleanser. Repetition for at least 2 weekly cycles, using careful technique, is needed. Suitable indications for these therapeutic options include proven resistance to available over-the-counter products in the community, a patient too young to use a pediculicide, or parental desire not to use a pediculicide.
* For children older than 6 months, benzyl alcohol 5% can be used in areas shown to have resistance to permethrin or pyrethrins or in patients with proven infestation refractory to appropriately administered treatment with permethrin or pyrethrins. In these situations, children at least 2 years old may be treated with malathion 0.5%.
* Safety and efficacy testing are recommended for new products.
* Appropriate training regarding the importance and difficulty of correctly diagnosing an active head lice infestation is needed for school personnel involved in detecting head lice infestation. School officials should review lice-related policies to ensure that this goal is achieved.
* Head lice screening programs have not been shown to be cost effective, nor have they been demonstrated to significantly reduce the incidence of head lice in the school setting with time. To manage head lice in the school setting, however, parent education programs may be helpful.
"The potential for misdiagnosis and the resulting improper use of pediculicides raise concerns about unsafe use of these products, specifically when no lice are present or when products are used excessively," the review authors write. "In addition, the emergence of resistance to available products and the development of new products, many without proof of efficacy or safety, call for increased physician involvement in the diagnosis and treatment of head lice."
"Optimal treatments are safe and effective, rapidly pediculicidal, ovicidal, easy to use, and affordable and incorporate a resistance-prevention strategy," the review authors conclude. "Because lice infestation is so benign, treatments must prove safe to ensure that the adverse effects of therapy are not worse than the infestation."
Pediatrics. Published online July 26, 2010.
Laurie Barclay, MD
July 26, 2010 — Current diagnosis, treatment protocols, and management guidelines regarding children with head lice in the school setting are presented in a clinical report posted online July 26 and in the August print issue of Pediatrics.
"Head lice infestation is associated with limited morbidity but causes a high level of anxiety among parents of school-aged children," write Barbara L. Frankowski, MD, MPH, and Joseph A. Bocchini Jr, MD, from the Council on School Health and Committee on Infectious Diseases, 2006-2010. "Since the 2002 clinical report on head lice was published by the American Academy of Pediatrics, patterns of resistance to products available over-the-counter and by prescription have changed, and additional mechanical means of removing head lice have been explored. This revised clinical report clarifies current diagnosis and treatment protocols and provides guidance for the management of children with head lice in the school setting."
The reference standard for diagnosing head lice is finding a live louse on the head, although infestation can also be diagnosed by using a louse comb or by observation of eggs at the nape of the neck or behind the ears, within 1 cm of the scalp.
Despite the impossibility of preventing all head lice infestations, children should be taught not to share personal items such as combs, brushes, and hats.
"Never initiate treatment unless there is a clear diagnosis of head lice," the review authors write. "The ideal treatment for lice would be completely safe, free of harmful chemicals, readily available without a prescription, easy to use, and inexpensive. When recommending a treatment, paediatricians should take into account effectiveness and safety, local patterns of resistance (if known), ease of use, and cost."
Specific Recommendations
Specific recommendations regarding current diagnosis, management, and treatment protocols for children with head lice in the school setting include the following:
* Head lice should not be a reason for an otherwise healthy child to be excluded from or kept absent from school. No-nit policies for return to school should therefore no longer be enforced.
* Pediatricians should know how to manage and treat head lice infestations so that they can actively inform families, schools, and other community agencies.
* For treatment of active infestations, 1% permethrin or pyrethrins are recommended unless resistance to these medications has been proven in the community.
* School staff and parents should be given detailed instructions on the proper use of recommended treatments. Current permethrin or pyrethrin products are not completely ovicidal, necessitating that they be applied at least twice at proper intervals. This is also recommended if live lice persist after treatment with malathion. To prevent spread, manual removal of nits is not necessary immediately after pediculicide therapy. However, nit removal may be considered in the school setting to reduce diagnostic confusion.
* Feasible alternatives to use of pediculicide may include "wet-combing" or an occlusive method, such as petroleum jelly or a mild skin cleanser. Repetition for at least 2 weekly cycles, using careful technique, is needed. Suitable indications for these therapeutic options include proven resistance to available over-the-counter products in the community, a patient too young to use a pediculicide, or parental desire not to use a pediculicide.
* For children older than 6 months, benzyl alcohol 5% can be used in areas shown to have resistance to permethrin or pyrethrins or in patients with proven infestation refractory to appropriately administered treatment with permethrin or pyrethrins. In these situations, children at least 2 years old may be treated with malathion 0.5%.
* Safety and efficacy testing are recommended for new products.
* Appropriate training regarding the importance and difficulty of correctly diagnosing an active head lice infestation is needed for school personnel involved in detecting head lice infestation. School officials should review lice-related policies to ensure that this goal is achieved.
* Head lice screening programs have not been shown to be cost effective, nor have they been demonstrated to significantly reduce the incidence of head lice in the school setting with time. To manage head lice in the school setting, however, parent education programs may be helpful.
"The potential for misdiagnosis and the resulting improper use of pediculicides raise concerns about unsafe use of these products, specifically when no lice are present or when products are used excessively," the review authors write. "In addition, the emergence of resistance to available products and the development of new products, many without proof of efficacy or safety, call for increased physician involvement in the diagnosis and treatment of head lice."
"Optimal treatments are safe and effective, rapidly pediculicidal, ovicidal, easy to use, and affordable and incorporate a resistance-prevention strategy," the review authors conclude. "Because lice infestation is so benign, treatments must prove safe to ensure that the adverse effects of therapy are not worse than the infestation."
Pediatrics. Published online July 26, 2010.
Sunday, July 25, 2010
Pediatric Educational Intervention May Reduce Prolonged Bottle Use
From MedscapeCME Clinical
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
July 13, 2010 — A simple educational intervention administered during a health maintenance visit reduces prolonged bottle use by 60% but does not reduce iron depletion at age 2 years, according to the results of a study reported online July 12 in Pediatrics.
"Observational studies suggest associations between prolonged bottle-feeding, excessive milk intake, and iron deficiency," write Jonathon L. Maguire, MD, MSc, from the University of Toronto in Ontario, Canada, and colleagues. "The [American Academy of Pediatrics] recommends complete bottle-weaning by 15 months, but many parents bottle-feed much longer. No evidence-based interventions exist to promote timely bottle-weaning."
The objective of this pragmatic, randomized trial was to assess the effect of an office-based, educational intervention for parents of 9-month-old children on reducing bottle use and iron depletion at age 2 years. During a routine health maintenance visit between January 2006 and January 2007, a total of 251 healthy, 9-month-old infants were randomly assigned to an intervention group (n = 129) or to a control group (n = 122).
In the intervention group, parents were introduced to a 1-week protocol designed to wean their child from bottle-feeding. The intervention could be administered in less than 5 minutes. Parents were given a sippy cup and taught how to use it to transition their child from the bottle, and they were also counseled regarding the risks for continued bottle use, including tooth decay, iron depletion, and poorer school performance. Study outcomes were iron depletion, defined as serum ferritin levels of 10 μg/L or less, and bottle use at age 2 years.
Follow-up rate was 81%, with 201 children monitored to age 2 years. In the intervention group, children began drinking from a cup 3 months earlier (9 vs 12 months; P = .001), were weaned from the bottle 4 months earlier (12 vs 16 months; P = .004), and were more than one half as likely to be using a bottle at age 2 years (15 [15%] of 102 children vs 39 [40%] of 99 children; P = .0004) vs the control group. However, the 2 groups were not significantly different at age 2 years in rates of iron depletion (10 [10%] of 102 children vs 13 [13%] of 99 children; P = .42) and in milk intake of more than 16 oz (16 [16%] of 102 children vs 17 [17%] of 99 children; P = .7).
"This simple intervention administered during a health maintenance visit did not result in a decrease in iron depletion at 2 years of age but did result in a 60% reduction in prolonged bottle use," the study authors write.
Limitations of this study include possibly insufficient power to show a reduction in iron depletion resulting from earlier bottle-weaning, risk for contamination between groups, and follow-up limited to age 2 years.
"Additional studies are needed to determine whether decreasing prolonged bottle use could lead to a reduction in iron depletion in higher-risk populations, as well as other proposed consequences of prolonged bottle-feeding, including bottle-related caries, otitis media, and behavior problems," the study authors conclude.
This study was supported by a grant-in-aid from the Danone Institute of Canada. The Pediatric Outcomes Research Team is supported by a grant from the Hospital for Sick Children Foundation. Dr. Maguire was supported by a Canadian Institutes of Health Research fellowship. The other study authors have disclosed no relevant financial relationships.
Pediatrics. Published online July 12, 2010.
Clinical Context
The American Academy of Pediatrics recommends that children be weaned off bottle feeding by age 15 months. There is an association between bottle feeding beyond ages 15 to 18 months and excessive milk intake and iron deficiency from observational studies. However, pediatricians do not routinely counsel parents to wean their children off bottles after age 15 months.
This is a prospective randomized study to compare rates of iron depletion and feeding behaviors with vs without an educational intervention for parents at a 9-month routine health maintenance visit.
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
July 13, 2010 — A simple educational intervention administered during a health maintenance visit reduces prolonged bottle use by 60% but does not reduce iron depletion at age 2 years, according to the results of a study reported online July 12 in Pediatrics.
"Observational studies suggest associations between prolonged bottle-feeding, excessive milk intake, and iron deficiency," write Jonathon L. Maguire, MD, MSc, from the University of Toronto in Ontario, Canada, and colleagues. "The [American Academy of Pediatrics] recommends complete bottle-weaning by 15 months, but many parents bottle-feed much longer. No evidence-based interventions exist to promote timely bottle-weaning."
The objective of this pragmatic, randomized trial was to assess the effect of an office-based, educational intervention for parents of 9-month-old children on reducing bottle use and iron depletion at age 2 years. During a routine health maintenance visit between January 2006 and January 2007, a total of 251 healthy, 9-month-old infants were randomly assigned to an intervention group (n = 129) or to a control group (n = 122).
In the intervention group, parents were introduced to a 1-week protocol designed to wean their child from bottle-feeding. The intervention could be administered in less than 5 minutes. Parents were given a sippy cup and taught how to use it to transition their child from the bottle, and they were also counseled regarding the risks for continued bottle use, including tooth decay, iron depletion, and poorer school performance. Study outcomes were iron depletion, defined as serum ferritin levels of 10 μg/L or less, and bottle use at age 2 years.
Follow-up rate was 81%, with 201 children monitored to age 2 years. In the intervention group, children began drinking from a cup 3 months earlier (9 vs 12 months; P = .001), were weaned from the bottle 4 months earlier (12 vs 16 months; P = .004), and were more than one half as likely to be using a bottle at age 2 years (15 [15%] of 102 children vs 39 [40%] of 99 children; P = .0004) vs the control group. However, the 2 groups were not significantly different at age 2 years in rates of iron depletion (10 [10%] of 102 children vs 13 [13%] of 99 children; P = .42) and in milk intake of more than 16 oz (16 [16%] of 102 children vs 17 [17%] of 99 children; P = .7).
"This simple intervention administered during a health maintenance visit did not result in a decrease in iron depletion at 2 years of age but did result in a 60% reduction in prolonged bottle use," the study authors write.
Limitations of this study include possibly insufficient power to show a reduction in iron depletion resulting from earlier bottle-weaning, risk for contamination between groups, and follow-up limited to age 2 years.
"Additional studies are needed to determine whether decreasing prolonged bottle use could lead to a reduction in iron depletion in higher-risk populations, as well as other proposed consequences of prolonged bottle-feeding, including bottle-related caries, otitis media, and behavior problems," the study authors conclude.
This study was supported by a grant-in-aid from the Danone Institute of Canada. The Pediatric Outcomes Research Team is supported by a grant from the Hospital for Sick Children Foundation. Dr. Maguire was supported by a Canadian Institutes of Health Research fellowship. The other study authors have disclosed no relevant financial relationships.
Pediatrics. Published online July 12, 2010.
Clinical Context
The American Academy of Pediatrics recommends that children be weaned off bottle feeding by age 15 months. There is an association between bottle feeding beyond ages 15 to 18 months and excessive milk intake and iron deficiency from observational studies. However, pediatricians do not routinely counsel parents to wean their children off bottles after age 15 months.
This is a prospective randomized study to compare rates of iron depletion and feeding behaviors with vs without an educational intervention for parents at a 9-month routine health maintenance visit.
Friday, July 23, 2010
For Childhood Cancer Survivors: New Data on Pregnancy Adverse Outcomes
From Medscape Medical News
Nick Mulcahy
July 22, 2010 — A new study of childhood cancer survivors provides information about the risks for stillbirth and neonatal death among the offspring of the survivors.
For the male survivors, there is good news: radiation to the testes did not affect the risk for these 2 adverse outcomes in their offspring.
For the female survivors overall, the data are sobering: radiation to the uterus and ovaries "greatly increased the risk of stillbirth and neonatal death."
However, the timing of the radiation to the pelvic region during childhood determined whether or not risk existed for women.
In women treated before menarche, various radiation doses were associated with as much as a 12-fold risk for stillbirth and neonatal death, report the study authors, led by Lisa B. Signorello, MD, from the International Epidemiology Institute in Rockville, Maryland, and the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.
On a bright note, in women treated after menarche, there was no significantly increased risk — no matter what the radiation dose.
The study of 1148 men and 1657 women who survived childhood cancer, and who between them had 4946 pregnancies, was published online July 23 in the Lancet.
The study population comes from the well-chronicled Childhood Cancer Survivor Study (CCSS), which involves 25 institutions in the United States and 1 in Canada.
The study authors say that genetic damage is not the cause of the misfortunate outcomes. They cite the null findings for male gonadal exposure to irradiation and other evidence to support this hypothesis. The adverse events for women survivors are "most likely attributable to uterine damage," they write.
The study advances the state of our understanding of pregnancy outcomes for female survivors, said an expert in childhood survivors of cancer who was not involved with study.
"The association between radiation to the pelvic region in childhood and adverse pregnancy outcomes, including stillbirths and neonatal deaths, in later life has been known for more than 20 years," Charles Sklar, MD, from Memorial Sloan-Kettering Cancer Center in New York City, told Medscape Medical News.
"The current Lancet study provides more precise estimates of risk and additional data on the interaction between age at treatment and the dose thresholds of radiation that are associated with these outcomes," he explained.
High-Risk Care Needed
Dr. Sklar suggested that all female survivors in their child-bearing years should be presented with this information.
"It is currently standard practice to provide this [risk] information to our patients who have been treated with pelvic radiation," he said.
If pregnant, the women also require special obstetrical care.
"For those women at risk who become pregnant, we currently advise — and will continue to recommend — that they seek care in a high-risk obstetrical practice/unit," said Dr. Sklar.
Chemotherapy Not Implicated
All patients in CCSS were younger than 21 years at initial diagnosis and had survived for at least 5 years after diagnosis. The most common cancers were leukemias and lymphomas (57%).
The investigators gathered data about pregnancy outcomes and childhood treatments from the survivors' medical records and from questionnaires mailed to the survivors.
In the study, the definition of a stillbirth was a fetal death after the 20th week of gestation; a neonatal death was defined as death within the first 28 days of life.
About two thirds of the study participants (1174 of 2805) were given radiotherapy as children (1042 males, 732 females). This group reported 60 stillbirths or neonatal deaths and 3077 live births.
Age at menarche was known or estimated for 90% of the women.
Women treated with radiation to the pelvic region after menarche had no significantly increased risk for stillbirths or neonatal deaths, compared with survivors who were not treated with radiation at all, say the authors.
Being treated with radiation to the pelvis before menarche was another story.
For mothers treated before menarche with radiation in doses of 1.00 to 2.49 Gy, the risk for stillbirth or neonatal death was 3 per 69 offspring (4%; relative risk [RR], 4.7; 95% confidence interval [CI], 1.2 - 19.0); for doses of 2.5 Gy or more, the risk was 11 per 82 offspring (13%; RR, 12.3; 95% CI, 4.2 - 36.0). In both cases, the risk was significantly increased (P = .0006).
There were not enough girls treated at high doses of radiation, so the exposure categories were not extended to 10 Gy or more, the authors point out.
In addition to evaluating women's risk associated with radiation to the pelvic region, the investigators looked at radiation to women's pituitary glands and to men's testes. Neither was found to have a positive association with risk for stillbirth or neonatal death.
The investigators also did not find an increased risk for stillbirth or neonatal death in the offspring of the men and women who had received chemotherapy with alkylating drugs, such as cisplatin and cyclophosphamide. Nor did they find any pattern of increasing dose with increasing risk.
These findings about chemotherapy repudiate concerns from other studies, suggest the authors.
"Treatment with alkylating drugs (mutagenic chemotherapy drugs) was thought to be a confounder of the association of radiation with stillbirths or neonatal deaths (and a potential independent risk factor for stillbirths and neonatal deaths)," they write.
The investigators received funding from the Westlakes Research Institute, the National Cancer Institute, and the Children's Cancer Research Fund.
Lancet. Published online July 23, 2010.
Nick Mulcahy
July 22, 2010 — A new study of childhood cancer survivors provides information about the risks for stillbirth and neonatal death among the offspring of the survivors.
For the male survivors, there is good news: radiation to the testes did not affect the risk for these 2 adverse outcomes in their offspring.
For the female survivors overall, the data are sobering: radiation to the uterus and ovaries "greatly increased the risk of stillbirth and neonatal death."
However, the timing of the radiation to the pelvic region during childhood determined whether or not risk existed for women.
In women treated before menarche, various radiation doses were associated with as much as a 12-fold risk for stillbirth and neonatal death, report the study authors, led by Lisa B. Signorello, MD, from the International Epidemiology Institute in Rockville, Maryland, and the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.
On a bright note, in women treated after menarche, there was no significantly increased risk — no matter what the radiation dose.
The study of 1148 men and 1657 women who survived childhood cancer, and who between them had 4946 pregnancies, was published online July 23 in the Lancet.
The study population comes from the well-chronicled Childhood Cancer Survivor Study (CCSS), which involves 25 institutions in the United States and 1 in Canada.
The study authors say that genetic damage is not the cause of the misfortunate outcomes. They cite the null findings for male gonadal exposure to irradiation and other evidence to support this hypothesis. The adverse events for women survivors are "most likely attributable to uterine damage," they write.
The study advances the state of our understanding of pregnancy outcomes for female survivors, said an expert in childhood survivors of cancer who was not involved with study.
"The association between radiation to the pelvic region in childhood and adverse pregnancy outcomes, including stillbirths and neonatal deaths, in later life has been known for more than 20 years," Charles Sklar, MD, from Memorial Sloan-Kettering Cancer Center in New York City, told Medscape Medical News.
"The current Lancet study provides more precise estimates of risk and additional data on the interaction between age at treatment and the dose thresholds of radiation that are associated with these outcomes," he explained.
High-Risk Care Needed
Dr. Sklar suggested that all female survivors in their child-bearing years should be presented with this information.
"It is currently standard practice to provide this [risk] information to our patients who have been treated with pelvic radiation," he said.
If pregnant, the women also require special obstetrical care.
"For those women at risk who become pregnant, we currently advise — and will continue to recommend — that they seek care in a high-risk obstetrical practice/unit," said Dr. Sklar.
Chemotherapy Not Implicated
All patients in CCSS were younger than 21 years at initial diagnosis and had survived for at least 5 years after diagnosis. The most common cancers were leukemias and lymphomas (57%).
The investigators gathered data about pregnancy outcomes and childhood treatments from the survivors' medical records and from questionnaires mailed to the survivors.
In the study, the definition of a stillbirth was a fetal death after the 20th week of gestation; a neonatal death was defined as death within the first 28 days of life.
About two thirds of the study participants (1174 of 2805) were given radiotherapy as children (1042 males, 732 females). This group reported 60 stillbirths or neonatal deaths and 3077 live births.
Age at menarche was known or estimated for 90% of the women.
Women treated with radiation to the pelvic region after menarche had no significantly increased risk for stillbirths or neonatal deaths, compared with survivors who were not treated with radiation at all, say the authors.
Being treated with radiation to the pelvis before menarche was another story.
For mothers treated before menarche with radiation in doses of 1.00 to 2.49 Gy, the risk for stillbirth or neonatal death was 3 per 69 offspring (4%; relative risk [RR], 4.7; 95% confidence interval [CI], 1.2 - 19.0); for doses of 2.5 Gy or more, the risk was 11 per 82 offspring (13%; RR, 12.3; 95% CI, 4.2 - 36.0). In both cases, the risk was significantly increased (P = .0006).
There were not enough girls treated at high doses of radiation, so the exposure categories were not extended to 10 Gy or more, the authors point out.
In addition to evaluating women's risk associated with radiation to the pelvic region, the investigators looked at radiation to women's pituitary glands and to men's testes. Neither was found to have a positive association with risk for stillbirth or neonatal death.
The investigators also did not find an increased risk for stillbirth or neonatal death in the offspring of the men and women who had received chemotherapy with alkylating drugs, such as cisplatin and cyclophosphamide. Nor did they find any pattern of increasing dose with increasing risk.
These findings about chemotherapy repudiate concerns from other studies, suggest the authors.
"Treatment with alkylating drugs (mutagenic chemotherapy drugs) was thought to be a confounder of the association of radiation with stillbirths or neonatal deaths (and a potential independent risk factor for stillbirths and neonatal deaths)," they write.
The investigators received funding from the Westlakes Research Institute, the National Cancer Institute, and the Children's Cancer Research Fund.
Lancet. Published online July 23, 2010.
Thursday, July 22, 2010
Study Links Zinc Nose Sprays, Loss of Smell
From WebMD Health News
Salynn Boyles
July 20, 2010 — Just over a year ago, the FDA warned that zinc-containing intranasal cold remedies might cause loss of sense of smell.
Now a researcher who has long argued that the sprays were harmful says he has scientific evidence to back up the claim.
Last summer, the FDA warned consumers to stop using three zinc-containing Zicam products: Zicam Cold Remedy Nasal Gel, Zicam Cold Remedy Swabs, and Zicam Cold Remedy Swabs for kids. The federal regulators cited 130 reports of loss of sense of smell among users of the products.
Zicam manufacturer Matrixx Initiatives pulled the three products from the shelves, but the company maintains that there is no link between their use and loss of smell.
In the newly reported analysis, researchers applied a statistical method used to establish a cause-and-effect link between an environmental exposure and development of a disease in an effort to confirm that zinc-containing nasal products can cause loss of sense of smell, known medically as anosmia.
University of California, San Diego professor Terence M. Davidson, MD, says the analysis supports the hypothesis.
He adds that the effectiveness of zinc-containing products for preventing or shortening the duration of colds has never been proven.
“Given that they do absolutely no good for colds and given that there is potential for harm, I see no point in putting any zinc gluconate products in the nose,” Davidson tells WebMD.
Zinc Sprays and Smell Loss
The analysis included 25 patients treated at the University of California, San Diego Nasal Dysfunction Clinic, which Davidson directs, who experienced loss of smell after using zinc nasal sprays or swabs to prevent or treat colds.
Along with colleague Wendy M. Smith, MD, Davidson applied the nine-point Bradford Hill causation environmental exposure statistical measure to assess the probability that the cold-remedy use caused the loss of sense of smell.
In lawsuits brought by Zicam users, Matrixx has maintained that loss of smell resulted from colds or sinus conditions and not use of the zinc-based nasal products.
Upper respiratory infections and nasal and sinus disease are major causes of both temporary and permanent loss of smell and diminished sense of smell.
Davidson says many of his patients and others with suspected zinc-induced smell loss reported intensely painful burning in the nose when they used the products. This was followed by loss of smell within several hours.
“This is a pain that brings people to their knees,” he says. “And soon after they get over the pain, they realize they can’t smell their coffee. This is very different from viral-induced anosmia.”
Courts Find Evidence Lacking
In an interview with WebMD, Matrixx CEO Bill Hemelt said there is no proven correlation between stinging and burning in people who used zinc nasal products and loss of sense of smell.
He notes that Matrixx’s own studies showed both zinc nasal spray and placebo sprays containing no zinc can cause occasional burning.
In 2006, Matrixx settled a lawsuit brought by 340 zinc-containing Zicam users for $12 million, and Hemelt says the company has settled other cases over the years.
But he adds that 10 judges in 10 cases have found little scientific evidence to support the claim that zinc-containing Zicam nasal products caused loss of smell.
In one such case, Davidson was rejected as an expert witness when the judge ruled his opinions on specific causation to be “seriously flawed.”
More than a dozen Zicam products remain on the market, including several oral zinc-based lozenges.
But none of the company’s nasal products still contain zinc gluconate.
“The products at issue were removed voluntarily more than a year ago,” Hemelt says. “There is absolutely no new scientific information in this analysis.”
Neurologist Robert I. Henkin, MD who directs the Taste and Smell Clinic in Washington, D.C., believes zinc-based nasal remedies can cause loss of sense of smell.
But he agrees that little scientific evidence exists to prove it.
“The most frequent cause of smell loss is the common cold,” he tells WebMD. “The role these zinc-based products play in initiating or exacerbating this condition remains very difficult to ascertain.”
Salynn Boyles
July 20, 2010 — Just over a year ago, the FDA warned that zinc-containing intranasal cold remedies might cause loss of sense of smell.
Now a researcher who has long argued that the sprays were harmful says he has scientific evidence to back up the claim.
Last summer, the FDA warned consumers to stop using three zinc-containing Zicam products: Zicam Cold Remedy Nasal Gel, Zicam Cold Remedy Swabs, and Zicam Cold Remedy Swabs for kids. The federal regulators cited 130 reports of loss of sense of smell among users of the products.
Zicam manufacturer Matrixx Initiatives pulled the three products from the shelves, but the company maintains that there is no link between their use and loss of smell.
In the newly reported analysis, researchers applied a statistical method used to establish a cause-and-effect link between an environmental exposure and development of a disease in an effort to confirm that zinc-containing nasal products can cause loss of sense of smell, known medically as anosmia.
University of California, San Diego professor Terence M. Davidson, MD, says the analysis supports the hypothesis.
He adds that the effectiveness of zinc-containing products for preventing or shortening the duration of colds has never been proven.
“Given that they do absolutely no good for colds and given that there is potential for harm, I see no point in putting any zinc gluconate products in the nose,” Davidson tells WebMD.
Zinc Sprays and Smell Loss
The analysis included 25 patients treated at the University of California, San Diego Nasal Dysfunction Clinic, which Davidson directs, who experienced loss of smell after using zinc nasal sprays or swabs to prevent or treat colds.
Along with colleague Wendy M. Smith, MD, Davidson applied the nine-point Bradford Hill causation environmental exposure statistical measure to assess the probability that the cold-remedy use caused the loss of sense of smell.
In lawsuits brought by Zicam users, Matrixx has maintained that loss of smell resulted from colds or sinus conditions and not use of the zinc-based nasal products.
Upper respiratory infections and nasal and sinus disease are major causes of both temporary and permanent loss of smell and diminished sense of smell.
Davidson says many of his patients and others with suspected zinc-induced smell loss reported intensely painful burning in the nose when they used the products. This was followed by loss of smell within several hours.
“This is a pain that brings people to their knees,” he says. “And soon after they get over the pain, they realize they can’t smell their coffee. This is very different from viral-induced anosmia.”
Courts Find Evidence Lacking
In an interview with WebMD, Matrixx CEO Bill Hemelt said there is no proven correlation between stinging and burning in people who used zinc nasal products and loss of sense of smell.
He notes that Matrixx’s own studies showed both zinc nasal spray and placebo sprays containing no zinc can cause occasional burning.
In 2006, Matrixx settled a lawsuit brought by 340 zinc-containing Zicam users for $12 million, and Hemelt says the company has settled other cases over the years.
But he adds that 10 judges in 10 cases have found little scientific evidence to support the claim that zinc-containing Zicam nasal products caused loss of smell.
In one such case, Davidson was rejected as an expert witness when the judge ruled his opinions on specific causation to be “seriously flawed.”
More than a dozen Zicam products remain on the market, including several oral zinc-based lozenges.
But none of the company’s nasal products still contain zinc gluconate.
“The products at issue were removed voluntarily more than a year ago,” Hemelt says. “There is absolutely no new scientific information in this analysis.”
Neurologist Robert I. Henkin, MD who directs the Taste and Smell Clinic in Washington, D.C., believes zinc-based nasal remedies can cause loss of sense of smell.
But he agrees that little scientific evidence exists to prove it.
“The most frequent cause of smell loss is the common cold,” he tells WebMD. “The role these zinc-based products play in initiating or exacerbating this condition remains very difficult to ascertain.”
Wednesday, July 21, 2010
Tdap Vaccine Protects Against Pertussis During Outbreak
From Reuters Health Information CME
News Author: Karla Gale, MS
CME Author: Penny Murata, MD
July 9, 2010 — The Tdap vaccine — a tetanus, reduced-dose diphtheria, and acellular pertussis booster — effectively protected adolescents during a pertussis outbreak in the U.S. Virgin Islands, investigators reported online June 25th in Clinical Infectious Diseases.
Tdap's licensure in 2005 was based on serological surrogate end points rather than direct vaccine efficacy data. In this study, the first published evaluation in an outbreak setting, Tdap was 65.6% effective.
The outbreak occurred in the autumn of 2007 at a nursery through 12th grade school on St. Croix. With 51 confirmed or probable cases among 499 students, the attack rate was 10%. Coughs lasted up to four months or more, with a median duration of 38 days.
According to senior author Dr. Stacey W. Martin, from the U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues, all but three cases occurred in grades six through 12, with an overall attack rate in those classes of 17%. The highest incidence was in the 10th grade (38%).
Among students age 11 and older, overall Tdap coverage was 12%. There were two confirmed or probable cases among 33 vaccinated students (6.1%) and 41 among 233 not vaccinated (17.6%, relative risk 2.9). The vaccine's effectiveness was not statistically significant (p = 0.092) due to limited sample size.
Local authorities collected nasopharyngeal aspirates or swab samples for culture and for pertussis polymerase chain reaction (PCR) testing from students whose cough had started no more than 14 days earlier. They also collected blood samples from students with any duration of cough. During the convalescence phase in winter 2008, nasopharyngeal specimens were again collected from kids with cough, and all students age 11 and over were offered serological testing regardless of cough history.
In confirmed cases, Bordetella pertussis was isolated in culture or patients had positive PCR or serological test results. Clinical cases (cough for at least 14 days along with whoop, post-tussive vomiting and/or paroxysmal cough) that were not laboratory-confirmed were classified as probable.
Because the Advisory Committee on Immunization Practices recommends Tdap vaccination only for adolescents and adults up to age 65, the research team limited its vaccine efficacy analyses to the 287 students age 11 and older.
Among 162 students who provided clinical specimens, six had culture-confirmed cases. These six also had the only positive results on PCR and convalescent serology.
The authors report that geometric mean concentrations (GMC) of anti-pertussis IgG varied in the serum samples obtained in the convalescent period, from 107.2 ELISA Units/mL in 40 patients with confirmed or probable cases, to 20.2 EU/mL in 45 students with a history of cough not meeting the case definition, and 29.4 EU/mL in 72 students with no history of cough (p < 0.001 comparing cases with noncases).
They also note that only 26 of 40 case patients had positive convalescent serological test results, and one had indeterminate results.
On the other hand, 12 of 72 noncoughing students also had positive serological test results, indicating "evidence of asymptomatic infection and the potential for unrecognized transmission."
The investigators also point out that serology results identified 20 patients who didn't present for testing until they'd been coughing for more than two weeks. These students didn't provide nasopharyngeal specimens, but if they had, the tests would likely have been negative because of the timing. Given the usefulness of serology in these cases, the authors recommend that the Council of State and Territorial Epidemiologists include serological testing in its case definition.
"Higher Tdap coverage rates are needed to minimize the negative impacts of waning immunity, imperfect (vaccine effectiveness) and high secondary transmission rates," the research team concludes.
Clin Infect Dis. 2010;51:315-321.
Reuters Health Information 2010. © 2010 Reuters Ltd.
Clinical Context
In the March 30, 2007, issue of MMWR. Morbidity and Mortality Weekly Report, McNabb and colleagues reported that 53% of pertussis cases in 2006 occurred in children at least 15 years old. According to Kretsinger and colleagues in the December 15, 2006, issue of MMWR. Recommendations and Reports: Morbidity and Mortality Weekly Report, a combined vaccine, Tdap, was recommended for all adolescents and adults up to age 65 years. In the March 2006 issue of Pediatrics, it was noted that approval of Tdap use was based on serologic responses in adolescents and adults.
This study of a pertussis outbreak assesses the vaccine effectiveness of Tdap and whether serologic testing is useful to detect pertussis.
News Author: Karla Gale, MS
CME Author: Penny Murata, MD
July 9, 2010 — The Tdap vaccine — a tetanus, reduced-dose diphtheria, and acellular pertussis booster — effectively protected adolescents during a pertussis outbreak in the U.S. Virgin Islands, investigators reported online June 25th in Clinical Infectious Diseases.
Tdap's licensure in 2005 was based on serological surrogate end points rather than direct vaccine efficacy data. In this study, the first published evaluation in an outbreak setting, Tdap was 65.6% effective.
The outbreak occurred in the autumn of 2007 at a nursery through 12th grade school on St. Croix. With 51 confirmed or probable cases among 499 students, the attack rate was 10%. Coughs lasted up to four months or more, with a median duration of 38 days.
According to senior author Dr. Stacey W. Martin, from the U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues, all but three cases occurred in grades six through 12, with an overall attack rate in those classes of 17%. The highest incidence was in the 10th grade (38%).
Among students age 11 and older, overall Tdap coverage was 12%. There were two confirmed or probable cases among 33 vaccinated students (6.1%) and 41 among 233 not vaccinated (17.6%, relative risk 2.9). The vaccine's effectiveness was not statistically significant (p = 0.092) due to limited sample size.
Local authorities collected nasopharyngeal aspirates or swab samples for culture and for pertussis polymerase chain reaction (PCR) testing from students whose cough had started no more than 14 days earlier. They also collected blood samples from students with any duration of cough. During the convalescence phase in winter 2008, nasopharyngeal specimens were again collected from kids with cough, and all students age 11 and over were offered serological testing regardless of cough history.
In confirmed cases, Bordetella pertussis was isolated in culture or patients had positive PCR or serological test results. Clinical cases (cough for at least 14 days along with whoop, post-tussive vomiting and/or paroxysmal cough) that were not laboratory-confirmed were classified as probable.
Because the Advisory Committee on Immunization Practices recommends Tdap vaccination only for adolescents and adults up to age 65, the research team limited its vaccine efficacy analyses to the 287 students age 11 and older.
Among 162 students who provided clinical specimens, six had culture-confirmed cases. These six also had the only positive results on PCR and convalescent serology.
The authors report that geometric mean concentrations (GMC) of anti-pertussis IgG varied in the serum samples obtained in the convalescent period, from 107.2 ELISA Units/mL in 40 patients with confirmed or probable cases, to 20.2 EU/mL in 45 students with a history of cough not meeting the case definition, and 29.4 EU/mL in 72 students with no history of cough (p < 0.001 comparing cases with noncases).
They also note that only 26 of 40 case patients had positive convalescent serological test results, and one had indeterminate results.
On the other hand, 12 of 72 noncoughing students also had positive serological test results, indicating "evidence of asymptomatic infection and the potential for unrecognized transmission."
The investigators also point out that serology results identified 20 patients who didn't present for testing until they'd been coughing for more than two weeks. These students didn't provide nasopharyngeal specimens, but if they had, the tests would likely have been negative because of the timing. Given the usefulness of serology in these cases, the authors recommend that the Council of State and Territorial Epidemiologists include serological testing in its case definition.
"Higher Tdap coverage rates are needed to minimize the negative impacts of waning immunity, imperfect (vaccine effectiveness) and high secondary transmission rates," the research team concludes.
Clin Infect Dis. 2010;51:315-321.
Reuters Health Information 2010. © 2010 Reuters Ltd.
Clinical Context
In the March 30, 2007, issue of MMWR. Morbidity and Mortality Weekly Report, McNabb and colleagues reported that 53% of pertussis cases in 2006 occurred in children at least 15 years old. According to Kretsinger and colleagues in the December 15, 2006, issue of MMWR. Recommendations and Reports: Morbidity and Mortality Weekly Report, a combined vaccine, Tdap, was recommended for all adolescents and adults up to age 65 years. In the March 2006 issue of Pediatrics, it was noted that approval of Tdap use was based on serologic responses in adolescents and adults.
This study of a pertussis outbreak assesses the vaccine effectiveness of Tdap and whether serologic testing is useful to detect pertussis.
Abused Children at Risk of Developing Psychiatric Disorders as Young Adults
From Medscape Medical News
Abused Children at Risk of Developing Psychiatric Disorders as Young Adults
Deborah Brauser
July 16, 2010 — Childhood abuse and neglect are significantly associated with increased rates of anxiety, mood, and substance use disorders in young adulthood, according to a new cohort study of more than 2000 participants from New Zealand.
Past research showing this association has relied heavily on retrospective reports of child maltreatment, whereas "the few" using prospective ascertainment have shown a weaker association, giving weight to the possibility that it is "the memory of maltreatment that raises the risk of later mental disorders," report the researchers.
However, this study showed that "maltreatment, not just memory of maltreatment, [was] associated with subsequent psychopathology," write lead author Kate Scott, PhD, senior lecturer and senior clinical psychologist in the Department of Psychological Medicine at the University of Otago-Wellington, New Zealand, and colleagues.
Therefore, "there is a need for both targeted mental health interventions with the present and past clients of child welfare agencies and for concerted population-level strategies to meet the needs of the many other children who experience maltreatment," add the study authors.
"Most clinicians are well aware of the effects of child abuse," Dr. Scott told Medscape Medical News. "The key message is for the research community...and for agencies with responsibility for the welfare of children — that they need to intervene to deal with the mental health effects of adverse environments in order to help prevent later disorders."
The study appears in the July issue of the Archives of General Psychiatry.
Reporting Retrospectively and Prospectively
The investigators examined data from 2144 respondents (between the ages of 16 and 27 years) to the Te Rau Hinengaro: New Zealand Mental Health Survey between the years 2003 and 2004. This survey used face-to-face interviews and included questions about sociodemographic information and some forms of child maltreatment (representing retrospective reporting).
It also included the World Mental Health–World Health Organization Composite International Diagnostic Interview to assess lifetime and 12-month prevalence of disorders based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria.
"Most [past] studies rely on adults to provide information on whether they were maltreated as children," said Dr. Scott. "Those retrospective reports are problematic because recall is not perfect and is affected by current mood, among other things, [which] might lead to a bias."
So 221 of the survey participants were also identified as having records on a New Zealand national child protection agency electronic database (representing prospectively ascertained child maltreatment).
In addition, "the odds ratios (ORs) were estimated first with the comparison group [those without a child protection agency record] inclusive of people retrospectively reporting child maltreatment and second, with the comparison group exclusive of people who retrospectively reported child maltreatment," explain the study authors.
Significant Risks for Disorders
Results showed that "after adjusting for demographic and socioeconomic correlates, child protection agency history was associated with several individual mental disorders, mental disorder comorbidity, and all mental disorder groups [at] both12-months and lifetime," report the authors.
The ORs were 5.12 for 12-month posttraumatic stress disorder (PTSD; 95% confidence interval [CI], 2.42 - 10.83), 2.41 for any anxiety disorder (95% CI, 1.47 - 3.97), 1.86 for any mood disorder (95% CI, 1.12 - 3.08), and 1.71 for any substance use disorder (95% CI, 1.01 - 2.88).
"These associations increased in magnitude when those who retrospectively reported child maltreatment were removed from the comparison group," write the study authors. This included an elevated OR of 10.92 for PTSD (95% CI, 4.38 - 27.22).
Finally, "the associations with 12-month mental disorder groups indicate that those in the child protection agency group still, after an average of 10 years since intervention to reduce maltreatment, have higher rates of mental disorder, with an approximately 3-fold increase in the odds of having multiple (≥3) disorders," the study authors report.
Important for the Field
"I think this study is tremendously important for the field," Katie McLaughlin, PhD, from the Harvard School of Public Health and the Department of Health Care Policy at Harvard Medical School in Boston, Massachusetts, told Medscape Medical News.
Dr. McLaughlin, who was not involved with this study but has recently written about the topic, noted that there has been increasing interest during the years in the role of adverse childhood experiences on health across the life course. "The majority of the research has been retrospective, which has raised some concerns. So I think this is really a critical paper in building the case for the importance of actual experiences as important determinants of a population's health."
When asked whether she had any concerns with the study, Dr. McLaughlin said that she sees it "as sort of a first paper, looking at the basic associations between maltreatment experiences and adult psychiatric disorders. I think there are a lot of questions that remain, and there's a lot I'd love to see [the investigators] do with this data. However, there's nothing that raises serious concerns for me about their general conclusions."
Overall, she noted that the study has "important implications" for both research and practice. "For the research community, I think it demonstrates that this association we see time and again in retrospective studies is most likely real and not a result of biases associated with distortions of memories or distorted reporting among people with mental disorders."
"For clinicians, I think the take-home message is that childhood maltreatment is something we need to be paying attention to very closely," added Dr. McLaughlin. "I don't think this is a surprise for people who work with kids. But the interesting point for clinicians who work with adults with mental disorders is that this is something important that we should be thinking about — that events that happen in childhood seem to have lasting effects in adulthood and may very well be relevant for addressing in therapy."
The New Zealand Mental Health Survey was supported by the Ministry of Health, the Alcohol Advisory Council of New Zealand, and the Health Research Council of New Zealand. The study authors have disclosed no relevant financial relationships..
Arch Gen Psychiatry. 2010;67:712-719. Abstract
Abused Children at Risk of Developing Psychiatric Disorders as Young Adults
Deborah Brauser
July 16, 2010 — Childhood abuse and neglect are significantly associated with increased rates of anxiety, mood, and substance use disorders in young adulthood, according to a new cohort study of more than 2000 participants from New Zealand.
Past research showing this association has relied heavily on retrospective reports of child maltreatment, whereas "the few" using prospective ascertainment have shown a weaker association, giving weight to the possibility that it is "the memory of maltreatment that raises the risk of later mental disorders," report the researchers.
However, this study showed that "maltreatment, not just memory of maltreatment, [was] associated with subsequent psychopathology," write lead author Kate Scott, PhD, senior lecturer and senior clinical psychologist in the Department of Psychological Medicine at the University of Otago-Wellington, New Zealand, and colleagues.
Therefore, "there is a need for both targeted mental health interventions with the present and past clients of child welfare agencies and for concerted population-level strategies to meet the needs of the many other children who experience maltreatment," add the study authors.
"Most clinicians are well aware of the effects of child abuse," Dr. Scott told Medscape Medical News. "The key message is for the research community...and for agencies with responsibility for the welfare of children — that they need to intervene to deal with the mental health effects of adverse environments in order to help prevent later disorders."
The study appears in the July issue of the Archives of General Psychiatry.
Reporting Retrospectively and Prospectively
The investigators examined data from 2144 respondents (between the ages of 16 and 27 years) to the Te Rau Hinengaro: New Zealand Mental Health Survey between the years 2003 and 2004. This survey used face-to-face interviews and included questions about sociodemographic information and some forms of child maltreatment (representing retrospective reporting).
It also included the World Mental Health–World Health Organization Composite International Diagnostic Interview to assess lifetime and 12-month prevalence of disorders based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria.
"Most [past] studies rely on adults to provide information on whether they were maltreated as children," said Dr. Scott. "Those retrospective reports are problematic because recall is not perfect and is affected by current mood, among other things, [which] might lead to a bias."
So 221 of the survey participants were also identified as having records on a New Zealand national child protection agency electronic database (representing prospectively ascertained child maltreatment).
In addition, "the odds ratios (ORs) were estimated first with the comparison group [those without a child protection agency record] inclusive of people retrospectively reporting child maltreatment and second, with the comparison group exclusive of people who retrospectively reported child maltreatment," explain the study authors.
Significant Risks for Disorders
Results showed that "after adjusting for demographic and socioeconomic correlates, child protection agency history was associated with several individual mental disorders, mental disorder comorbidity, and all mental disorder groups [at] both12-months and lifetime," report the authors.
The ORs were 5.12 for 12-month posttraumatic stress disorder (PTSD; 95% confidence interval [CI], 2.42 - 10.83), 2.41 for any anxiety disorder (95% CI, 1.47 - 3.97), 1.86 for any mood disorder (95% CI, 1.12 - 3.08), and 1.71 for any substance use disorder (95% CI, 1.01 - 2.88).
"These associations increased in magnitude when those who retrospectively reported child maltreatment were removed from the comparison group," write the study authors. This included an elevated OR of 10.92 for PTSD (95% CI, 4.38 - 27.22).
Finally, "the associations with 12-month mental disorder groups indicate that those in the child protection agency group still, after an average of 10 years since intervention to reduce maltreatment, have higher rates of mental disorder, with an approximately 3-fold increase in the odds of having multiple (≥3) disorders," the study authors report.
Important for the Field
"I think this study is tremendously important for the field," Katie McLaughlin, PhD, from the Harvard School of Public Health and the Department of Health Care Policy at Harvard Medical School in Boston, Massachusetts, told Medscape Medical News.
Dr. McLaughlin, who was not involved with this study but has recently written about the topic, noted that there has been increasing interest during the years in the role of adverse childhood experiences on health across the life course. "The majority of the research has been retrospective, which has raised some concerns. So I think this is really a critical paper in building the case for the importance of actual experiences as important determinants of a population's health."
When asked whether she had any concerns with the study, Dr. McLaughlin said that she sees it "as sort of a first paper, looking at the basic associations between maltreatment experiences and adult psychiatric disorders. I think there are a lot of questions that remain, and there's a lot I'd love to see [the investigators] do with this data. However, there's nothing that raises serious concerns for me about their general conclusions."
Overall, she noted that the study has "important implications" for both research and practice. "For the research community, I think it demonstrates that this association we see time and again in retrospective studies is most likely real and not a result of biases associated with distortions of memories or distorted reporting among people with mental disorders."
"For clinicians, I think the take-home message is that childhood maltreatment is something we need to be paying attention to very closely," added Dr. McLaughlin. "I don't think this is a surprise for people who work with kids. But the interesting point for clinicians who work with adults with mental disorders is that this is something important that we should be thinking about — that events that happen in childhood seem to have lasting effects in adulthood and may very well be relevant for addressing in therapy."
The New Zealand Mental Health Survey was supported by the Ministry of Health, the Alcohol Advisory Council of New Zealand, and the Health Research Council of New Zealand. The study authors have disclosed no relevant financial relationships..
Arch Gen Psychiatry. 2010;67:712-719. Abstract
Tuesday, July 20, 2010
IVF Associated With Increased Risk for Childhood Cancer
From Medscape Medical News
IVF Associated With Increased Risk for Childhood Cancer
Nick Mulcahy
July 20, 2010 — Children born after in vitro fertilization (IVF) are at a "moderately" increased risk of developing childhood cancer, according to a population-based study from Sweden published online July 19 in Pediatrics.
The study, which is the largest to date, is the first to show that the increased risk is statistically significant.
The researchers compared 26,692 children born after IVF with a control group of 2.4 million children not conceived by IVF between 1982 and 2005.
They identified 53 cases of cancer in children who were born after IVF (38 cases were expected). The total cancer risk estimate was 1.42 (95% confidence interval [CI], 1.09 - 1.87; P = .01).
"It should be stressed that the individual risk for a child who is born after IVF to develop childhood cancer is low," write the authors, led by Bengt Källén, MD, PhD, from the Tornblad Institute of the University of Lund in Sweden.
Dr. Källén and colleagues do not believe that IVF itself is the likely cause of the risk.
"This is probably not attributable to the IVF procedure itself but could be an effect of confounding from unidentified characteristics of women who undergo IVF or could act via the widely known increased risks for neonatal complication," they write.
The increased risk for perinatal complications from IVF births includes congenital malformations, the authors point out.
The study is actually an outgrowth of a previous study by the same Swedish researchers. In the earlier study (Fertil Steril. 2005;84:605-610), there were fewer children born after IVF and less follow-up time. That study found nearly the same risk estimate (1.41), but the result was not statistically significant (95% CI, 0.98 - 2.03).
Statistics Include Langerhans Cell Histiocytosis
Among the 53 cases of cancer found in the study, the individual cancers were as follows:
* 18 infants had hematologic neoplasms (12.3 expected), 15 of which were acute lymphoblastic leukemia
* 15 infants had central nervous system neoplasms (8.1 expected), 7 of which were astrocytomas
* 2 infants had malignant retinal tumors (retinoblastoma) (1.25 expected)
* 6 infants had Langerhans cell histiocytosis (1 expected).
After adjustment for year of birth, the odds ratio for childhood cancer among infants who were born after IVF was 1.42.
The researchers acknowledge that the classification of Langerhans cell histiocytosis as a cancer is debatable: "Is it a malignant neoplastic disease or a reactive process?"
"Little is known about the epidemiology of Langerhans histiocytosis," the authors write.
Therefore, they performed an analysis of the total cancer risk that excluded the children with histiocytosis and found that the odds ratio went down to 1.34 — but remained statistically significant.
What's Driving the Increased Risk?
The investigators observed that the mothers of children born after IVF differed in many ways from the 2.4 million other women who gave birth in the study: maternal age was higher, there was a high percentage of first parity, fewer smoked, more had a high body mass index, and fewer were born outside Sweden.
Neither the differences between the 2 sets of mothers nor adjustment for these differences had any impact on the estimated risk, report the study authors, but neonatal characteristics did affect cancer risk.
There was an increased risk for cancer associated with preterm birth before week 37, a birth weight of 4500 g of higher, and a low Apgar score.
"Neonatal factors could act as intermediaries between the IVF procedure and cancer development," write the authors.
They also note that, in various studies, 2 neonatal factors have shown a "relatively constant association" with an increased childhood cancer risk: high birth weight and neonatal asphyxia.
Both factors were seen in this study. Neonatal asphyxia or oxygen treatment was indicated in the study by a low Apgar score.
Multiple births, which are a common complication in IVF pregnancies, did not seem to factor into the cancer risk in the study, report the authors.
The study was supported by a grant from the Evy and Gunnar Sandberg Foundation in Lund. The authors have disclosed no relevant financial relationships.
Pediatrics. 2010;126:e270-e276.
IVF Associated With Increased Risk for Childhood Cancer
Nick Mulcahy
July 20, 2010 — Children born after in vitro fertilization (IVF) are at a "moderately" increased risk of developing childhood cancer, according to a population-based study from Sweden published online July 19 in Pediatrics.
The study, which is the largest to date, is the first to show that the increased risk is statistically significant.
The researchers compared 26,692 children born after IVF with a control group of 2.4 million children not conceived by IVF between 1982 and 2005.
They identified 53 cases of cancer in children who were born after IVF (38 cases were expected). The total cancer risk estimate was 1.42 (95% confidence interval [CI], 1.09 - 1.87; P = .01).
"It should be stressed that the individual risk for a child who is born after IVF to develop childhood cancer is low," write the authors, led by Bengt Källén, MD, PhD, from the Tornblad Institute of the University of Lund in Sweden.
Dr. Källén and colleagues do not believe that IVF itself is the likely cause of the risk.
"This is probably not attributable to the IVF procedure itself but could be an effect of confounding from unidentified characteristics of women who undergo IVF or could act via the widely known increased risks for neonatal complication," they write.
The increased risk for perinatal complications from IVF births includes congenital malformations, the authors point out.
The study is actually an outgrowth of a previous study by the same Swedish researchers. In the earlier study (Fertil Steril. 2005;84:605-610), there were fewer children born after IVF and less follow-up time. That study found nearly the same risk estimate (1.41), but the result was not statistically significant (95% CI, 0.98 - 2.03).
Statistics Include Langerhans Cell Histiocytosis
Among the 53 cases of cancer found in the study, the individual cancers were as follows:
* 18 infants had hematologic neoplasms (12.3 expected), 15 of which were acute lymphoblastic leukemia
* 15 infants had central nervous system neoplasms (8.1 expected), 7 of which were astrocytomas
* 2 infants had malignant retinal tumors (retinoblastoma) (1.25 expected)
* 6 infants had Langerhans cell histiocytosis (1 expected).
After adjustment for year of birth, the odds ratio for childhood cancer among infants who were born after IVF was 1.42.
The researchers acknowledge that the classification of Langerhans cell histiocytosis as a cancer is debatable: "Is it a malignant neoplastic disease or a reactive process?"
"Little is known about the epidemiology of Langerhans histiocytosis," the authors write.
Therefore, they performed an analysis of the total cancer risk that excluded the children with histiocytosis and found that the odds ratio went down to 1.34 — but remained statistically significant.
What's Driving the Increased Risk?
The investigators observed that the mothers of children born after IVF differed in many ways from the 2.4 million other women who gave birth in the study: maternal age was higher, there was a high percentage of first parity, fewer smoked, more had a high body mass index, and fewer were born outside Sweden.
Neither the differences between the 2 sets of mothers nor adjustment for these differences had any impact on the estimated risk, report the study authors, but neonatal characteristics did affect cancer risk.
There was an increased risk for cancer associated with preterm birth before week 37, a birth weight of 4500 g of higher, and a low Apgar score.
"Neonatal factors could act as intermediaries between the IVF procedure and cancer development," write the authors.
They also note that, in various studies, 2 neonatal factors have shown a "relatively constant association" with an increased childhood cancer risk: high birth weight and neonatal asphyxia.
Both factors were seen in this study. Neonatal asphyxia or oxygen treatment was indicated in the study by a low Apgar score.
Multiple births, which are a common complication in IVF pregnancies, did not seem to factor into the cancer risk in the study, report the authors.
The study was supported by a grant from the Evy and Gunnar Sandberg Foundation in Lund. The authors have disclosed no relevant financial relationships.
Pediatrics. 2010;126:e270-e276.
Friday, July 16, 2010
Using the Genetics of Smoking Behavior to Optimize Selection of Cessation Technique
From Medscape Genomic Medicine > Genomics in Practice
Jacquelyn K. Beals, PhD
posted 6/23/2010
If you are among the thousands of people who have tried to quit smoking, you may have done an Internet search on "smoking cessation" and "techniques." The approaches seem endless (> 500,000 results), and the promised outcomes questionable. But at least one of them should work for you, right?
Neurolinguistic programming claims to remove the psychological craving to smoke, and aversion therapy conditions smokers to associate smoking with unpleasant stimuli. A hypnotherapy site promises that clients will leave after an hour as "happy nonsmokers," while an acupuncturist more modestly says that treatment will "decrease withdrawal symptoms and the desire for cigarettes." And the list goes on.
The common factor in these claims is behavior modification. But is the tendency to smoke, to become nicotine-addicted, and to have difficulty quitting primarily behavioral -- a product of social surroundings and custom -- or is it genetic? Studies in twins have shown that between 40% and 60% of differences in smoking cessation are genetic.[1] Are some smokers, no matter how sincere their attempts to quit, doomed to failure, whereas others can go "cold turkey" with relative ease?
Where There's Smoke, There's CHRNA
Persistent smokers, whether clinicians or patients, may be interested in 3 studies published in the May 2010 issue of Nature Genetics.[2-4] The first report, from the Tobacco and Genetics Consortium,[2] is a meta-analysis of genetic results from more than 74,000 individuals and focused on the "15 most significant regions" associated with smoking. Their results identify 3 gene variants highly associated with cigarettes smoked per day (CPD) -- a recognized measure of nicotine addiction.
Chief among these is a variant of the nicotinic receptor gene CHRNA3. Three other single-nucleotide polymorphisms (SNPs) demonstrate much lower genome-wide significance; among them, EGLN2 codes for an enzyme involved in hypoxia-inducible factor degradation, the activity of which varies with oxygen availability.
Eight SNPs were associated with smoking initiation. The most significant is BDNF, a gene variously implicated in adult synaptic plasticity and in the effectiveness of antidepressants. A lone SNP near DBH (whose product catalyzes conversion of dopamine to norepinephrine) was associated with smoking cessation.
The second study, by the Oxford-GlaxoSmithKline study group,[3] reported a genome-wide meta-analysis of SNPs associated with behavioral traits related to smoking, using a study population of 41,150. CPD was tightly associated with several CHRNA genes, including CHRNA3. The study's search for genetic variants associated with establishing a smoking habit, or with past smoking but successful quitting, found no genome-wide significance or inconsistent results, respectively.
Finally, a group headed by deCODE Genetics[4] focused its study on CPD and smoking initiation. Their genome-wide meta-analysis found strong associations between CPD and SNPs in the region containing members of the CHRN gene family. CPD was also significantly associated with SNPs on chromosomes 19 and 8, including genes encoding enzymes that metabolize nicotine.
I'd Walk a Mile for Some Dopamine
It's all very well to note the prominent and consistently replicated association between CPD and variants encoding nicotinic receptors, but how can these findings guide clinical practice? A glance at earlier studies that focus on "addictive personalities" suggests some potential applications.
A 2007 study in Science [5] linked reduced dopamine receptor density and high dopamine levels with a poor ability to learn from errors. Specifically, reduced density of dopamine receptor D2 is associated with addictive behaviors; individuals with a genetic polymorphism that reduces D2 receptor density show less avoidance learning and relatively more learning from positive reinforcement.
Thus, failure to quit smoking may not always be caused by "needy" nicotinic receptors, but it could also reflect an inability to learn from negative outcomes. Perhaps it is not a coincidence that in the 3 recent studies the only SNP to be associated with smoking cessation lies near DBH, the product of which catalyzes dopamine conversion to norepinephrine.
A second study with even greater clinical relevance appeared in 2008 in Archives of General Psychiatry.[6] Smokers between 18 and 65 years of age were placed in one of several clinical smoking cessation trials evaluating bupropion vs placebo, nicotine nasal spray vs nicotine patch, nicotine patch vs placebo, or bupropion vs placebo.
Genetic analyses searched for SNPs associated with successful abstention throughout the trials. Although the investigators identified a long list of genes with variants that distinguished between successful and unsuccessful quitters, they concluded that the genetic factors involved in smoking cessation were different for the dopamine transporter blocker bupropion than for any of the nicotine replacement therapies.
I Screen, You Screen, We All Screen for ... What?
The complexity of human smoking behavior will probably never be reduced to a game where nicotine trumps dopamine or vice versa. However, as researchers continue to find gene variants associated with establishing a smoking habit, CPD, and successful or unsuccessful cessation, clinicians can use this information to accommodate patients' individual differences.
For example, if a patient's genomic profile shows CHRNA variants associated with high CPD, nicotine craving is probably a strong factor and nicotine replacement therapy may help that patient quit smoking. By contrast, a patient whose genomic screening reveals the variant that reduces dopamine receptor density probably learns poorly from negative feedback but relatively better through positive reinforcement. For this patient, the "carrots" of a positive reinforcement program may be more effective than the "sticks" of aversion therapy -- and unquestionably healthier than the carcinogen-laden "sticks" that they replace.
References
Jacquelyn K. Beals, PhD
posted 6/23/2010
If you are among the thousands of people who have tried to quit smoking, you may have done an Internet search on "smoking cessation" and "techniques." The approaches seem endless (> 500,000 results), and the promised outcomes questionable. But at least one of them should work for you, right?
Neurolinguistic programming claims to remove the psychological craving to smoke, and aversion therapy conditions smokers to associate smoking with unpleasant stimuli. A hypnotherapy site promises that clients will leave after an hour as "happy nonsmokers," while an acupuncturist more modestly says that treatment will "decrease withdrawal symptoms and the desire for cigarettes." And the list goes on.
The common factor in these claims is behavior modification. But is the tendency to smoke, to become nicotine-addicted, and to have difficulty quitting primarily behavioral -- a product of social surroundings and custom -- or is it genetic? Studies in twins have shown that between 40% and 60% of differences in smoking cessation are genetic.[1] Are some smokers, no matter how sincere their attempts to quit, doomed to failure, whereas others can go "cold turkey" with relative ease?
Where There's Smoke, There's CHRNA
Persistent smokers, whether clinicians or patients, may be interested in 3 studies published in the May 2010 issue of Nature Genetics.[2-4] The first report, from the Tobacco and Genetics Consortium,[2] is a meta-analysis of genetic results from more than 74,000 individuals and focused on the "15 most significant regions" associated with smoking. Their results identify 3 gene variants highly associated with cigarettes smoked per day (CPD) -- a recognized measure of nicotine addiction.
Chief among these is a variant of the nicotinic receptor gene CHRNA3. Three other single-nucleotide polymorphisms (SNPs) demonstrate much lower genome-wide significance; among them, EGLN2 codes for an enzyme involved in hypoxia-inducible factor degradation, the activity of which varies with oxygen availability.
Eight SNPs were associated with smoking initiation. The most significant is BDNF, a gene variously implicated in adult synaptic plasticity and in the effectiveness of antidepressants. A lone SNP near DBH (whose product catalyzes conversion of dopamine to norepinephrine) was associated with smoking cessation.
The second study, by the Oxford-GlaxoSmithKline study group,[3] reported a genome-wide meta-analysis of SNPs associated with behavioral traits related to smoking, using a study population of 41,150. CPD was tightly associated with several CHRNA genes, including CHRNA3. The study's search for genetic variants associated with establishing a smoking habit, or with past smoking but successful quitting, found no genome-wide significance or inconsistent results, respectively.
Finally, a group headed by deCODE Genetics[4] focused its study on CPD and smoking initiation. Their genome-wide meta-analysis found strong associations between CPD and SNPs in the region containing members of the CHRN gene family. CPD was also significantly associated with SNPs on chromosomes 19 and 8, including genes encoding enzymes that metabolize nicotine.
I'd Walk a Mile for Some Dopamine
It's all very well to note the prominent and consistently replicated association between CPD and variants encoding nicotinic receptors, but how can these findings guide clinical practice? A glance at earlier studies that focus on "addictive personalities" suggests some potential applications.
A 2007 study in Science [5] linked reduced dopamine receptor density and high dopamine levels with a poor ability to learn from errors. Specifically, reduced density of dopamine receptor D2 is associated with addictive behaviors; individuals with a genetic polymorphism that reduces D2 receptor density show less avoidance learning and relatively more learning from positive reinforcement.
Thus, failure to quit smoking may not always be caused by "needy" nicotinic receptors, but it could also reflect an inability to learn from negative outcomes. Perhaps it is not a coincidence that in the 3 recent studies the only SNP to be associated with smoking cessation lies near DBH, the product of which catalyzes dopamine conversion to norepinephrine.
A second study with even greater clinical relevance appeared in 2008 in Archives of General Psychiatry.[6] Smokers between 18 and 65 years of age were placed in one of several clinical smoking cessation trials evaluating bupropion vs placebo, nicotine nasal spray vs nicotine patch, nicotine patch vs placebo, or bupropion vs placebo.
Genetic analyses searched for SNPs associated with successful abstention throughout the trials. Although the investigators identified a long list of genes with variants that distinguished between successful and unsuccessful quitters, they concluded that the genetic factors involved in smoking cessation were different for the dopamine transporter blocker bupropion than for any of the nicotine replacement therapies.
I Screen, You Screen, We All Screen for ... What?
The complexity of human smoking behavior will probably never be reduced to a game where nicotine trumps dopamine or vice versa. However, as researchers continue to find gene variants associated with establishing a smoking habit, CPD, and successful or unsuccessful cessation, clinicians can use this information to accommodate patients' individual differences.
For example, if a patient's genomic profile shows CHRNA variants associated with high CPD, nicotine craving is probably a strong factor and nicotine replacement therapy may help that patient quit smoking. By contrast, a patient whose genomic screening reveals the variant that reduces dopamine receptor density probably learns poorly from negative feedback but relatively better through positive reinforcement. For this patient, the "carrots" of a positive reinforcement program may be more effective than the "sticks" of aversion therapy -- and unquestionably healthier than the carcinogen-laden "sticks" that they replace.
References
Tuesday, July 13, 2010
Children's health, Teen Pregnancies, Prem labor
From WebMD Health News
Premature Birth Rate Is Dropping
Bill Hendrick
July 13, 2010 — The rate of premature births has dropped slightly for the second year in a row, according to a new federal report.
What is more, the rate of births to teens also has declined, the study shows.
The report, "America's Children in Brief: Key National Indicators of Well-Being, 2010," finds that in the period 2007-2008:
* The percentage of infants born preterm (before 37 weeks) dropped from 12.7% to 12.3%.
* Teen girls are having fewer babies. Births to adolescents dropped from 22.2 per 1,000 girls to 21.7.
* The rate of children 17 years and under covered by health insurance at some time during the year rose from 89% to 90%.
* The percentage of children 17 and under who are living with at least one parent employed full-time dropped from 77% to 75%.
* The percentage of children 17 and under living in "food insecure" homes rose from 17% to 22%, the highest prevalence since monitoring began. The report defines "food security" as having access at all times to enough food for all family members to lead active, healthy lives.
"The decline in preterm births is encouraging," Alan E. Guttmacher, MD, acting director of the Eunice Kennedy Shriver National Institute of Child Health and Development, says in a news release. "Preterm infants are at higher risk for death in the first year of life, for serious illness in infancy, and in later life, for obesity and its associated complications."
Edward Sondik, PhD, director of the CDC's National Center for Health Statistics, says in the same news release that the decline in births to teens is significant because it occurred after two years of increases.
Reading and Math Improvements
The report also shows improvements in children's education, including higher reading and math scores for eighth graders. In the period from 2007 to 2009:
* Eighth graders' average mathematics scores increased from 281 to 283 on one scale of measurement, while fourth graders' scores were flat after rising for a number of years.
* Eighth graders' average reading scores also increased, from 263 to 264, while scores of fourth graders did not change.
* From 2008 to 2009, the percentage of teens 16-19 who were neither enrolled in school nor working increased from 8% to 9%. Black and Hispanic young people were more likely to be in that situation than white teens.
Guttmacher said in a telephone news briefing that the federal report presents 40 indicators of child well-being, including family and social environment, economic circumstances, health care, physical environment and safety, behavior, education, and health.
He says the drop in preterm births was mostly in later pregnancy -- those that occur at 34-36 weeks of gestation.
He says it's unclear why the rate of preterm births dropped, but that this matter is being investigated with a view toward further reducing the preterm birth rate.
Sondik says the decline in preterm births was seen in each of the three largest racial and ethnic groups, and that though small, "even a slight decrease in preterm birth is positive."
Despite improvements, however, he says about 136,000 babies were born to mothers 15-27 in 2008.
Unmarried Mothers
The research also sheds light on trends for unmarried mothers:
* Children born to single mothers are at a higher risk for adverse consequences, such as being born at a low birth weight and living in poverty.
* 41% of all births in 2008 were to unmarried mothers, up from 40% in 2007 and more than double the percentage of 30 years ago.
* Though the number and percentage of all births to unmarried women have increased, the birth rate among unmarried women 15-44 decreased from 53 births for every 1,000 unmarried women in 2007 to 52 in 2008. The decrease is attributable to the fact that the total number of unmarried women in that age range increased.
* 9% of children under 18 in 2008 had asthma, unchanged from 2007.
* During 2007-2008, 19% of children 6-17 were obese, about the same as the 2005-2006 period.
* In 2008, some 69% of recent high school grads had enrolled in college the fall after getting their diplomas, considerably higher than 49% in 1980.
* The percentage of children 5-11 years old with untreated dental cavities declined from 27% in 1999-2004 to 20% in 2005-2008.
* For youths 12-17 years old, the percentage with untreated dental cavities declined from 19% to 12% in the same two time periods.
"Looking at the data by income status for children in poverty, the percentage with untreated cavities was twice that of children who lived in families with incomes at or above 200% of the poverty level," Sondik says. "However, the percentage with untreated cavities declined across the board for all income levels."
The obesity rate for children today is triple what it was from 1976 to 1980, Sondik says.
He also points out that the percentage of teens who regularly smoke cigarettes is at its lowest level since data collection began in 1980.
In 2009, less than 3% of eighth graders reported smoking cigarettes every day, down from 10% in the mid-1990s. He says 6% of 10th graders smoked in 2009, about a third the rate of the mid-1990s, and 11% of 12th graders smoked daily, down from 25% in 1997.
In 2008, the researchers say, 90% of young adults had a high school diploma or an equivalent credential, up from 84% in 1980.
SOURCES:
News release, National Institutes of Health.
Premature Birth Rate Is Dropping
Bill Hendrick
July 13, 2010 — The rate of premature births has dropped slightly for the second year in a row, according to a new federal report.
What is more, the rate of births to teens also has declined, the study shows.
The report, "America's Children in Brief: Key National Indicators of Well-Being, 2010," finds that in the period 2007-2008:
* The percentage of infants born preterm (before 37 weeks) dropped from 12.7% to 12.3%.
* Teen girls are having fewer babies. Births to adolescents dropped from 22.2 per 1,000 girls to 21.7.
* The rate of children 17 years and under covered by health insurance at some time during the year rose from 89% to 90%.
* The percentage of children 17 and under who are living with at least one parent employed full-time dropped from 77% to 75%.
* The percentage of children 17 and under living in "food insecure" homes rose from 17% to 22%, the highest prevalence since monitoring began. The report defines "food security" as having access at all times to enough food for all family members to lead active, healthy lives.
"The decline in preterm births is encouraging," Alan E. Guttmacher, MD, acting director of the Eunice Kennedy Shriver National Institute of Child Health and Development, says in a news release. "Preterm infants are at higher risk for death in the first year of life, for serious illness in infancy, and in later life, for obesity and its associated complications."
Edward Sondik, PhD, director of the CDC's National Center for Health Statistics, says in the same news release that the decline in births to teens is significant because it occurred after two years of increases.
Reading and Math Improvements
The report also shows improvements in children's education, including higher reading and math scores for eighth graders. In the period from 2007 to 2009:
* Eighth graders' average mathematics scores increased from 281 to 283 on one scale of measurement, while fourth graders' scores were flat after rising for a number of years.
* Eighth graders' average reading scores also increased, from 263 to 264, while scores of fourth graders did not change.
* From 2008 to 2009, the percentage of teens 16-19 who were neither enrolled in school nor working increased from 8% to 9%. Black and Hispanic young people were more likely to be in that situation than white teens.
Guttmacher said in a telephone news briefing that the federal report presents 40 indicators of child well-being, including family and social environment, economic circumstances, health care, physical environment and safety, behavior, education, and health.
He says the drop in preterm births was mostly in later pregnancy -- those that occur at 34-36 weeks of gestation.
He says it's unclear why the rate of preterm births dropped, but that this matter is being investigated with a view toward further reducing the preterm birth rate.
Sondik says the decline in preterm births was seen in each of the three largest racial and ethnic groups, and that though small, "even a slight decrease in preterm birth is positive."
Despite improvements, however, he says about 136,000 babies were born to mothers 15-27 in 2008.
Unmarried Mothers
The research also sheds light on trends for unmarried mothers:
* Children born to single mothers are at a higher risk for adverse consequences, such as being born at a low birth weight and living in poverty.
* 41% of all births in 2008 were to unmarried mothers, up from 40% in 2007 and more than double the percentage of 30 years ago.
* Though the number and percentage of all births to unmarried women have increased, the birth rate among unmarried women 15-44 decreased from 53 births for every 1,000 unmarried women in 2007 to 52 in 2008. The decrease is attributable to the fact that the total number of unmarried women in that age range increased.
* 9% of children under 18 in 2008 had asthma, unchanged from 2007.
* During 2007-2008, 19% of children 6-17 were obese, about the same as the 2005-2006 period.
* In 2008, some 69% of recent high school grads had enrolled in college the fall after getting their diplomas, considerably higher than 49% in 1980.
* The percentage of children 5-11 years old with untreated dental cavities declined from 27% in 1999-2004 to 20% in 2005-2008.
* For youths 12-17 years old, the percentage with untreated dental cavities declined from 19% to 12% in the same two time periods.
"Looking at the data by income status for children in poverty, the percentage with untreated cavities was twice that of children who lived in families with incomes at or above 200% of the poverty level," Sondik says. "However, the percentage with untreated cavities declined across the board for all income levels."
The obesity rate for children today is triple what it was from 1976 to 1980, Sondik says.
He also points out that the percentage of teens who regularly smoke cigarettes is at its lowest level since data collection began in 1980.
In 2009, less than 3% of eighth graders reported smoking cigarettes every day, down from 10% in the mid-1990s. He says 6% of 10th graders smoked in 2009, about a third the rate of the mid-1990s, and 11% of 12th graders smoked daily, down from 25% in 1997.
In 2008, the researchers say, 90% of young adults had a high school diploma or an equivalent credential, up from 84% in 1980.
SOURCES:
News release, National Institutes of Health.
Monday, July 12, 2010
CDC Issues Updated Guidelines for Testing for Tuberculosis Infection
From MedscapeCME Clinical Briefs
MMWR Morb Mortal Wkly Rep. 2010;59(RR-5):1-28.
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
CME Released: 06/30/2010
Clinical Context
Approximately one third of the world's population has latent tuberculosis infection, although the rate of latent tuberculosis has declined significantly during the last 30 years in the United States.
The lifetime risk for active tuberculosis among patients with a history of a positive tuberculin skin test result is between 5% to 10%, although the rate of active tuberculosis has also declined in the United States in the last decade.
Identifying patients with either active or latent tuberculosis infection is a public health priority, and the introduction of IGRAs may advance this effort.
IGRAs detect sensitization to M tuberculosis by measuring interferon gamma release in response to antigens presenting on M tuberculosis.
The current guidelines describe the accuracy of IGRAs and offer recommendations for the use of these assays.
Study Highlights
* 4 IGRAs have been approved by the FDA for testing for tuberculosis. Assessing the accuracy of these tests is difficult because there is no "gold standard" to confirm latent tuberculosis infection or culture-negative tuberculosis.
* The sensitivity of the QFT-GIT test was 81% in detecting culture-confirmed active tuberculosis, whereas the pooled sensitivity for the T-Spot test was 91%. Both of these tests appear roughly similar to the tuberculin skin test in sensitivity to detect active tuberculosis.
* IGRAs are expected to be more specific than the tuberculin skin test because of reduced bias in interpretation and no interaction with the BCG vaccine. The pooled specificity values of QFT-GIT and T-Spot are 99% and 86%, respectively.
* Some research has suggested that IGRAs may be superior to tuberculin skin tests in diagnosing recent tuberculosis infections, whereas skin tests can be better in diagnosing remote infection. However, these studies are not unequivocal.
* IGRAs appear similar to the tuberculin skin test in predicting subsequent active tuberculosis.
* Few performance data exist for IGRA testing in children, particularly in high-risk children younger than 5 years.
* Limited data suggest that IGRAs are at least as accurate as tuberculin skin testing in detecting tuberculosis among immunocompromised persons.
* The authors recommend that IGRAs may be better than tuberculin skin tests among patients who are less likely to return for the reading of their skin tests (eg, among homeless individuals or patients who abuse drugs) and among those who previously received the BCG vaccine.
* Tuberculin skin testing is recommended vs IGRAs among children younger than 5 years.
* Either IGRAs or tuberculin skin testing may be used at the practitioners' discretion to test persons with recent contact with cases of active tuberculosis. Either test is also applicable to individuals with possible tuberculosis exposure in their workplace.
* In most cases, IGRAs and tuberculin skin tests should not be performed in the same person. Both tests may be done in high-risk cases in which the initial testing result was negative (probable false-negative) or in very low-risk cases with a positive initial test (probable false-positive).
* Neither test should generally be used among persons with a low risk for infection who are also unlikely to progress to active tuberculosis.
Clinical Implications
* The current recommendations suggest that IGRAs have a similar sensitivity but a greater specificity in diagnosing tuberculosis vs the tuberculin skin test.
* The current recommendations suggest that IGRAs are preferred vs tuberculin skin testing when the patient is less likely to return for reading of the skin test, or when the patient previously received the BCG vaccine. The tuberculin skin test remains preferred vs IGRAs among children younger than 5 years.
MMWR Morb Mortal Wkly Rep. 2010;59(RR-5):1-28.
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
CME Released: 06/30/2010
Clinical Context
Approximately one third of the world's population has latent tuberculosis infection, although the rate of latent tuberculosis has declined significantly during the last 30 years in the United States.
The lifetime risk for active tuberculosis among patients with a history of a positive tuberculin skin test result is between 5% to 10%, although the rate of active tuberculosis has also declined in the United States in the last decade.
Identifying patients with either active or latent tuberculosis infection is a public health priority, and the introduction of IGRAs may advance this effort.
IGRAs detect sensitization to M tuberculosis by measuring interferon gamma release in response to antigens presenting on M tuberculosis.
The current guidelines describe the accuracy of IGRAs and offer recommendations for the use of these assays.
Study Highlights
* 4 IGRAs have been approved by the FDA for testing for tuberculosis. Assessing the accuracy of these tests is difficult because there is no "gold standard" to confirm latent tuberculosis infection or culture-negative tuberculosis.
* The sensitivity of the QFT-GIT test was 81% in detecting culture-confirmed active tuberculosis, whereas the pooled sensitivity for the T-Spot test was 91%. Both of these tests appear roughly similar to the tuberculin skin test in sensitivity to detect active tuberculosis.
* IGRAs are expected to be more specific than the tuberculin skin test because of reduced bias in interpretation and no interaction with the BCG vaccine. The pooled specificity values of QFT-GIT and T-Spot are 99% and 86%, respectively.
* Some research has suggested that IGRAs may be superior to tuberculin skin tests in diagnosing recent tuberculosis infections, whereas skin tests can be better in diagnosing remote infection. However, these studies are not unequivocal.
* IGRAs appear similar to the tuberculin skin test in predicting subsequent active tuberculosis.
* Few performance data exist for IGRA testing in children, particularly in high-risk children younger than 5 years.
* Limited data suggest that IGRAs are at least as accurate as tuberculin skin testing in detecting tuberculosis among immunocompromised persons.
* The authors recommend that IGRAs may be better than tuberculin skin tests among patients who are less likely to return for the reading of their skin tests (eg, among homeless individuals or patients who abuse drugs) and among those who previously received the BCG vaccine.
* Tuberculin skin testing is recommended vs IGRAs among children younger than 5 years.
* Either IGRAs or tuberculin skin testing may be used at the practitioners' discretion to test persons with recent contact with cases of active tuberculosis. Either test is also applicable to individuals with possible tuberculosis exposure in their workplace.
* In most cases, IGRAs and tuberculin skin tests should not be performed in the same person. Both tests may be done in high-risk cases in which the initial testing result was negative (probable false-negative) or in very low-risk cases with a positive initial test (probable false-positive).
* Neither test should generally be used among persons with a low risk for infection who are also unlikely to progress to active tuberculosis.
Clinical Implications
* The current recommendations suggest that IGRAs have a similar sensitivity but a greater specificity in diagnosing tuberculosis vs the tuberculin skin test.
* The current recommendations suggest that IGRAs are preferred vs tuberculin skin testing when the patient is less likely to return for reading of the skin test, or when the patient previously received the BCG vaccine. The tuberculin skin test remains preferred vs IGRAs among children younger than 5 years.
Parenting a VLBW Child May Have Both Positive and Negative Outcomes
Arch Pediatr Adolesc Med. 2010;164:518-524. Abstract
Clinical Context
VLBW and extremely LBW infants are increasing, with more than 63,000 annually in the United States. Family stress and financial burden are higher, with maternal coping strategies also adversely affected.
This is a longitudinal study of mothers of VLBW vs term infants to examine the maternal impact associated with having a VLBW child.
Study Highlights
* The study included high-risk and low-risk VLBW and term infants born in a US city between 1989 and 1992.
* Mothers and children were followed up at 7 time points for assessment: ages 1 and 8 months, and 1, 2, 3, 8, and 14 years.
* Children with VLBW were categorized as high risk or low risk.
* High-risk VLBW children had a diagnosis of bronchopulmonary dysplasia, had a birth weight less than 1500 g, required supplemental oxygen for 28 days or more, and had radiologically proven chronic lung disease.
* Low-risk VLBW infants did not have a diagnosis of bronchopulmonary dysplasia, had a birth weight of less than 1500 g, and required oxygen supplementation for less than 25 days.
* Excluded were infants with congenital malformations, whose mothers had alcohol exposure during pregnancy, psychiatric illness, HIV, or mental retardation.
* Also excluded were 4 infants in whom cancer subsequently developed.
* The cohort consisted of 113 high-risk, 80 low-risk, and 122 term infants, of whom 78% were seen at 4 or more visits at the duration of follow-up.
* Mothers completed several questionnaires at the follow-up visits.
* The Parenting Stress Index measured parental perceptions of stress related to child-rearing including 7 dimensions of stress (attachment, depression, role restriction, health, sense of competence, social isolation, and partner support) and child characteristics.
* The Stress Index for Parents of Adolescents (the adolescent version of the Parenting Stress Index) was given at 14 years.
* The Impact on Family Scale measures maternal perceptions of the child's negative and positive impact on the family, including financial impact.
* The Multidimensional Scale of Perceived Social Support, measured at 2 to 14 years, assessed the mother's perceived support from friends, family, and significant other.
* The Peabody Picture Vocabulary Test–Revised at infant birth was administered to mothers at all visits.
* All children were administered standardized normative IQ and developmental assessments at each visit including the Bayley Scales of Infant Development and the Wechsler Intelligence Scale for Children for IQ.
* High-risk VLBW infants had lower birth and gestational ages, more neurologic and medical risk factors at birth, and lower IQs at 8 years vs low-risk VLBW and term infants.
* IQ scores were less than 70 (intellectual disability) for 22% of high-risk VLBW, 10% of low-risk VLBW, and 3% of term infants.
* Mothers of term infants increased their educational level at a faster rate vs mothers of high-risk and low-risk VLBW infants and by 14 years had attained significantly more years of education (14.51 vs 13.82 years; P = .04).
* Mothers did not differ in use of coping mechanisms from birth through 3 years.
* However, mothers of high-risk VLBW infants reduced use of mental disengagement and denial from 8 to 14 years, resulting in lower use vs mothers of low-risk VLBW and term infants.
* Social support was similar for all groups during follow-up.
* Mothers of high-risk VLBW infants reported more financial stress, but the effect was neutralized when they had high levels of social support.
* High-risk VLBW birth was associated with higher child-related stress, mediated by lower IQ.
* However, by 14 years, mothers of high-risk VLBW infants had lower child-related stress than mothers of both low-risk VLBW and term infants.
* The authors concluded that mothers of high-risk VLBW infants were less likely to advance in education and to experience higher financial stress under situations of low social support.
* However, they noted that mothers of high-risk VLBW infants adapted their coping mechanisms and were less likely than mothers of low-risk VLBW and term infants to use mental disengagement and denial for coping, demonstrating resilience to having a VLBW child.
* They suggested that mothers of VLBW infants with low social support be provided with greater monitoring and help.
Clinical Implications
* Mothers of high-risk VLBW infants attain fewer years of education by 14 years after birth than mothers of term infants.
* Mothers of high-risk VLBW infants are less likely to use disengagement and denial as coping mechanisms by 8 years after birth.
Clinical Context
VLBW and extremely LBW infants are increasing, with more than 63,000 annually in the United States. Family stress and financial burden are higher, with maternal coping strategies also adversely affected.
This is a longitudinal study of mothers of VLBW vs term infants to examine the maternal impact associated with having a VLBW child.
Study Highlights
* The study included high-risk and low-risk VLBW and term infants born in a US city between 1989 and 1992.
* Mothers and children were followed up at 7 time points for assessment: ages 1 and 8 months, and 1, 2, 3, 8, and 14 years.
* Children with VLBW were categorized as high risk or low risk.
* High-risk VLBW children had a diagnosis of bronchopulmonary dysplasia, had a birth weight less than 1500 g, required supplemental oxygen for 28 days or more, and had radiologically proven chronic lung disease.
* Low-risk VLBW infants did not have a diagnosis of bronchopulmonary dysplasia, had a birth weight of less than 1500 g, and required oxygen supplementation for less than 25 days.
* Excluded were infants with congenital malformations, whose mothers had alcohol exposure during pregnancy, psychiatric illness, HIV, or mental retardation.
* Also excluded were 4 infants in whom cancer subsequently developed.
* The cohort consisted of 113 high-risk, 80 low-risk, and 122 term infants, of whom 78% were seen at 4 or more visits at the duration of follow-up.
* Mothers completed several questionnaires at the follow-up visits.
* The Parenting Stress Index measured parental perceptions of stress related to child-rearing including 7 dimensions of stress (attachment, depression, role restriction, health, sense of competence, social isolation, and partner support) and child characteristics.
* The Stress Index for Parents of Adolescents (the adolescent version of the Parenting Stress Index) was given at 14 years.
* The Impact on Family Scale measures maternal perceptions of the child's negative and positive impact on the family, including financial impact.
* The Multidimensional Scale of Perceived Social Support, measured at 2 to 14 years, assessed the mother's perceived support from friends, family, and significant other.
* The Peabody Picture Vocabulary Test–Revised at infant birth was administered to mothers at all visits.
* All children were administered standardized normative IQ and developmental assessments at each visit including the Bayley Scales of Infant Development and the Wechsler Intelligence Scale for Children for IQ.
* High-risk VLBW infants had lower birth and gestational ages, more neurologic and medical risk factors at birth, and lower IQs at 8 years vs low-risk VLBW and term infants.
* IQ scores were less than 70 (intellectual disability) for 22% of high-risk VLBW, 10% of low-risk VLBW, and 3% of term infants.
* Mothers of term infants increased their educational level at a faster rate vs mothers of high-risk and low-risk VLBW infants and by 14 years had attained significantly more years of education (14.51 vs 13.82 years; P = .04).
* Mothers did not differ in use of coping mechanisms from birth through 3 years.
* However, mothers of high-risk VLBW infants reduced use of mental disengagement and denial from 8 to 14 years, resulting in lower use vs mothers of low-risk VLBW and term infants.
* Social support was similar for all groups during follow-up.
* Mothers of high-risk VLBW infants reported more financial stress, but the effect was neutralized when they had high levels of social support.
* High-risk VLBW birth was associated with higher child-related stress, mediated by lower IQ.
* However, by 14 years, mothers of high-risk VLBW infants had lower child-related stress than mothers of both low-risk VLBW and term infants.
* The authors concluded that mothers of high-risk VLBW infants were less likely to advance in education and to experience higher financial stress under situations of low social support.
* However, they noted that mothers of high-risk VLBW infants adapted their coping mechanisms and were less likely than mothers of low-risk VLBW and term infants to use mental disengagement and denial for coping, demonstrating resilience to having a VLBW child.
* They suggested that mothers of VLBW infants with low social support be provided with greater monitoring and help.
Clinical Implications
* Mothers of high-risk VLBW infants attain fewer years of education by 14 years after birth than mothers of term infants.
* Mothers of high-risk VLBW infants are less likely to use disengagement and denial as coping mechanisms by 8 years after birth.
Sunday, July 11, 2010
MMRV Doubles Risk for Febrile Seizures 7 to 10 Days After Vaccination
From MedscapeCME Clinical Briefs
News Author: Pauline Anderson
CME Author: Charles P. Vega, MD
June 30, 2010 — Infants aged 12 to 23 months have about double the risk of developing a febrile seizure for 7 to 10 days after being vaccinated with the measles-mumps-rubella-varicella (MMRV) combination vaccine compared with those receiving separate MMR and varicella vaccines, according to a new study.
Despite this increase, physicians and parents should understand that the overall risk for febrile seizures from either the MMR or MMRV vaccine is low, stressed lead study author Nicola P. Klein, MD, PhD, codirector of the Kaiser Permanente Vaccine Study Center in Oakland, California.
"The risk is less than 1 per 1000 doses, but the risk is twice as much for febrile seizures for MMRV when you compare it with MMR and varicella," Dr. Klein said. "The MMRV will cause 1 additional febrile seizure for every 2300 doses of MMRV given instead of the separate vaccine.”
The study appears in the July 2010 issue of Pediatrics and was published online June 28.
Double the Data
For the study, researchers used electronic health records from the Vaccine Safety Datalink (VSD), a collaborative effort between the Centers for Disease Control and Prevention Immunization Safety Office and 8 managed care organizations across the country. The analysis included data on 459,000 children who had been vaccinated — 83,000 with the MMRV vaccine and 376,000 with the MMR plus varicella vaccines — from 2000 to 2008.
The MMRV vaccine was licensed by the US Food and Drug Administration (FDA) in 2005. Shortly after that, the VSD began actively monitoring the safety of new vaccines, including the MMRV vaccine, explained Dr. Klein. Preliminary studies showed a roughly 2-fold increased rate of seizures with this combination vaccine compared with the separate vaccines — information that was reported to the Advisory Committee on Immunization Practices in February 2008.
Since then, they've doubled the available data on the MMRV vaccine, said Dr. Klein. "Also, when we originally reported in 2008, we just looked at the 7 to 10 days after vaccination; since then, we've looked at the entire 42 days after vaccination and found that the febrile seizure risk is confined to just the 7- to 10-day window."
According to background information in the study, the VSD creates aggregated dynamic data sets that are updated weekly and contain vaccine information and outcomes. MMRV rapid cycle analysis surveillance monitored children 12 to 23 months old for 6 outcomes. In addition to seizures, outcomes of interest included thrombocytopenia, encephalitis or meningitis, ataxia, allergic reactions, and arthritis.
The researchers compared the cumulative number of seizures observed with the number expected on the basis of the historical VSD seizure rates from 2000 to 2006 after MMR vaccine was administered with or without varicella. They examined postvaccination outpatient fever visits for fever or febrile illness at 7 participating VSD sites from January 2000 to October 2008.
Seizures were defined according to the International Classification of Diseases, Ninth Revision. To assess whether postvaccination seizures were febrile seizures, researchers conducted medical record reviews. When available, they also captured data on previous seizure history, family history of seizures, and whether the seizure resulted in hospitalization.
For the primary analysis, as well as for 3 supplementary analyses, researchers adjusted for age group, site, calendar year, and respiratory virus season.
Seizure Peak
The study found that seizure incidence peaked during the period days 7 to 10 after vaccination with all measles-containing vaccines. Primary analysis revealed significantly higher seizure risk after MMRV vaccination than after MMR plus varicella vaccination during this time (relative risk, 1.98; 95% confidence interval [CI], 1.43 – 2.73).
"What we found in our study is that when you take combination vaccine — measles, mumps, rubella, and varicella — in the combination vaccine, there's a doubling of the risk for febrile seizures when you compare them with children who received separate MMR and varicella vaccines," said Dr. Klein.
MMRV vaccination was associated with an estimated 4.3 additional seizures per 10,000 doses (95% CI, 2.6 – 5.6) during the 7 to 10 days after vaccination. This translates into about 1 additional febrile seizure for every 2300 MMRV doses administered to 12- to 23-month-olds instead of separately administered same-day MMR plus varicella vaccination.
Medical record reviews verified 94% of electronically identified seizures as acute seizures, with 87% being febrile seizures. Using case-centered analyses strengthened the results because they addressed confounding caused by coding or diagnostic practices, data error, patient demographics, or care-seeking behavior, said the study authors.
The study results "show that both MMRV and MMR vaccines, but not varicella vaccine alone, are associated with increased outpatient fever visits and seizures 7 to 10 days after vaccination, with MMRV vaccine increasing fever and seizure twice as much as the MMR plus varicella vaccines," said the study authors. "MMRV vaccine doubles an already elevated risk for febrile seizures."
Dr. Klein pointed out that febrile seizures are common but usually harmless in children. "Up to 5% of children 6 months to 5 years of age can have a febrile seizure, and they are almost always due to colds or other infections. These seizures are a benign condition and they self-resolve. They don't have any long-term side effects; they don't, for example, lead to seizures and they don't lead to epilepsy."
However, they can be alarming. "The seizures can be very frightening for parents," said Dr. Klein. "Typically, it's a full-body convulsion and so parents do bring [the] child to the emergency department."
Pediatric Academy Statement
Asked to comment on the research, John Bradley, MD, a member of the American Academy of Pediatrics (AAP) Committee on Infectious Disease, director of the Division of Infectious Diseases at Rady Children's Hospital, and associate clinical professor of pediatrics, University of California at San Diego, said the AAP supports both vaccines equally.
However, the increased risk for febrile seizures with the MMRV vaccine should be shared with parents. "You should then let them make the decision. If you can't communicate with them because of a language barrier or other reason, you should give the vaccines separately to minimize risks of adverse events."
Dr. Bradley agreed that some parents would still opt for the combined vaccine. "Some prefer the convenience of just coming to the doctor and getting 1 vaccine rather than 2 shots for their kids, but we want them to have that option."
He added that when the MMRV vaccine was first approved by the FDA, "we knew that there was a little bit of extra fever but at that time the repercussion of that extra fever, meaning febrile seizures, was not yet defined."
The AAP is preparing a statement on this issue, which should be released in a month, if not before, said Dr. Bradley.
Dr. Bradley reiterated that febrile seizures are usually "very brief" and benign. "They're not known to produce any neurological injury. If the seizures were horrible and children ended up with injury, we would not be recommending this vaccine."
However, they could be a burden on the healthcare system. The AAP is carrying out an analysis of the extra costs associated with visits to general practitioners and neurologists and trips to the emergency department because of vaccine-related febrile seizures, said Dr. Bradley.
It is not clear exactly why there is increased fever with the combination vaccine. It could be because this vaccine needs extra varicella virus to produce the same immune response as the separate vaccines, said Dr. Bradley.
This study was supported by the VSD contract with America's Health Insurance Plans, funded by the Centers for Disease Control and Prevention. Dr. Klein and Roger Baxter, MD, have reported research support from Merck & Co, Novartis, GlaxoSmithKline, Wyeth, and Sanofi-Pasteur; the other study authors have disclosed no relevant financial relationships.
Pediatrics. Published online June 28, 2010.
Clinical Context
The MMRV vaccine was licensed by the FDA in 2005. The combination of the MMR and varicella vaccines affords the promise of similar immune protection against important infections with a reduction in the number of injections, which young children need to endure. However, prelicensure studies of the MMRV revealed that it promoted higher rates of fever and measles-like rash in the 1 to 2 weeks after vaccination vs separate MMR and varicella vaccines.
There has also been evidence that the combined MMRV vaccine may promote a higher risk for seizures vs the separate MMR and varicella vaccines. The current study analyzes data from the VSD to address this issue.
News Author: Pauline Anderson
CME Author: Charles P. Vega, MD
June 30, 2010 — Infants aged 12 to 23 months have about double the risk of developing a febrile seizure for 7 to 10 days after being vaccinated with the measles-mumps-rubella-varicella (MMRV) combination vaccine compared with those receiving separate MMR and varicella vaccines, according to a new study.
Despite this increase, physicians and parents should understand that the overall risk for febrile seizures from either the MMR or MMRV vaccine is low, stressed lead study author Nicola P. Klein, MD, PhD, codirector of the Kaiser Permanente Vaccine Study Center in Oakland, California.
"The risk is less than 1 per 1000 doses, but the risk is twice as much for febrile seizures for MMRV when you compare it with MMR and varicella," Dr. Klein said. "The MMRV will cause 1 additional febrile seizure for every 2300 doses of MMRV given instead of the separate vaccine.”
The study appears in the July 2010 issue of Pediatrics and was published online June 28.
Double the Data
For the study, researchers used electronic health records from the Vaccine Safety Datalink (VSD), a collaborative effort between the Centers for Disease Control and Prevention Immunization Safety Office and 8 managed care organizations across the country. The analysis included data on 459,000 children who had been vaccinated — 83,000 with the MMRV vaccine and 376,000 with the MMR plus varicella vaccines — from 2000 to 2008.
The MMRV vaccine was licensed by the US Food and Drug Administration (FDA) in 2005. Shortly after that, the VSD began actively monitoring the safety of new vaccines, including the MMRV vaccine, explained Dr. Klein. Preliminary studies showed a roughly 2-fold increased rate of seizures with this combination vaccine compared with the separate vaccines — information that was reported to the Advisory Committee on Immunization Practices in February 2008.
Since then, they've doubled the available data on the MMRV vaccine, said Dr. Klein. "Also, when we originally reported in 2008, we just looked at the 7 to 10 days after vaccination; since then, we've looked at the entire 42 days after vaccination and found that the febrile seizure risk is confined to just the 7- to 10-day window."
According to background information in the study, the VSD creates aggregated dynamic data sets that are updated weekly and contain vaccine information and outcomes. MMRV rapid cycle analysis surveillance monitored children 12 to 23 months old for 6 outcomes. In addition to seizures, outcomes of interest included thrombocytopenia, encephalitis or meningitis, ataxia, allergic reactions, and arthritis.
The researchers compared the cumulative number of seizures observed with the number expected on the basis of the historical VSD seizure rates from 2000 to 2006 after MMR vaccine was administered with or without varicella. They examined postvaccination outpatient fever visits for fever or febrile illness at 7 participating VSD sites from January 2000 to October 2008.
Seizures were defined according to the International Classification of Diseases, Ninth Revision. To assess whether postvaccination seizures were febrile seizures, researchers conducted medical record reviews. When available, they also captured data on previous seizure history, family history of seizures, and whether the seizure resulted in hospitalization.
For the primary analysis, as well as for 3 supplementary analyses, researchers adjusted for age group, site, calendar year, and respiratory virus season.
Seizure Peak
The study found that seizure incidence peaked during the period days 7 to 10 after vaccination with all measles-containing vaccines. Primary analysis revealed significantly higher seizure risk after MMRV vaccination than after MMR plus varicella vaccination during this time (relative risk, 1.98; 95% confidence interval [CI], 1.43 – 2.73).
"What we found in our study is that when you take combination vaccine — measles, mumps, rubella, and varicella — in the combination vaccine, there's a doubling of the risk for febrile seizures when you compare them with children who received separate MMR and varicella vaccines," said Dr. Klein.
MMRV vaccination was associated with an estimated 4.3 additional seizures per 10,000 doses (95% CI, 2.6 – 5.6) during the 7 to 10 days after vaccination. This translates into about 1 additional febrile seizure for every 2300 MMRV doses administered to 12- to 23-month-olds instead of separately administered same-day MMR plus varicella vaccination.
Medical record reviews verified 94% of electronically identified seizures as acute seizures, with 87% being febrile seizures. Using case-centered analyses strengthened the results because they addressed confounding caused by coding or diagnostic practices, data error, patient demographics, or care-seeking behavior, said the study authors.
The study results "show that both MMRV and MMR vaccines, but not varicella vaccine alone, are associated with increased outpatient fever visits and seizures 7 to 10 days after vaccination, with MMRV vaccine increasing fever and seizure twice as much as the MMR plus varicella vaccines," said the study authors. "MMRV vaccine doubles an already elevated risk for febrile seizures."
Dr. Klein pointed out that febrile seizures are common but usually harmless in children. "Up to 5% of children 6 months to 5 years of age can have a febrile seizure, and they are almost always due to colds or other infections. These seizures are a benign condition and they self-resolve. They don't have any long-term side effects; they don't, for example, lead to seizures and they don't lead to epilepsy."
However, they can be alarming. "The seizures can be very frightening for parents," said Dr. Klein. "Typically, it's a full-body convulsion and so parents do bring [the] child to the emergency department."
Pediatric Academy Statement
Asked to comment on the research, John Bradley, MD, a member of the American Academy of Pediatrics (AAP) Committee on Infectious Disease, director of the Division of Infectious Diseases at Rady Children's Hospital, and associate clinical professor of pediatrics, University of California at San Diego, said the AAP supports both vaccines equally.
However, the increased risk for febrile seizures with the MMRV vaccine should be shared with parents. "You should then let them make the decision. If you can't communicate with them because of a language barrier or other reason, you should give the vaccines separately to minimize risks of adverse events."
Dr. Bradley agreed that some parents would still opt for the combined vaccine. "Some prefer the convenience of just coming to the doctor and getting 1 vaccine rather than 2 shots for their kids, but we want them to have that option."
He added that when the MMRV vaccine was first approved by the FDA, "we knew that there was a little bit of extra fever but at that time the repercussion of that extra fever, meaning febrile seizures, was not yet defined."
The AAP is preparing a statement on this issue, which should be released in a month, if not before, said Dr. Bradley.
Dr. Bradley reiterated that febrile seizures are usually "very brief" and benign. "They're not known to produce any neurological injury. If the seizures were horrible and children ended up with injury, we would not be recommending this vaccine."
However, they could be a burden on the healthcare system. The AAP is carrying out an analysis of the extra costs associated with visits to general practitioners and neurologists and trips to the emergency department because of vaccine-related febrile seizures, said Dr. Bradley.
It is not clear exactly why there is increased fever with the combination vaccine. It could be because this vaccine needs extra varicella virus to produce the same immune response as the separate vaccines, said Dr. Bradley.
This study was supported by the VSD contract with America's Health Insurance Plans, funded by the Centers for Disease Control and Prevention. Dr. Klein and Roger Baxter, MD, have reported research support from Merck & Co, Novartis, GlaxoSmithKline, Wyeth, and Sanofi-Pasteur; the other study authors have disclosed no relevant financial relationships.
Pediatrics. Published online June 28, 2010.
Clinical Context
The MMRV vaccine was licensed by the FDA in 2005. The combination of the MMR and varicella vaccines affords the promise of similar immune protection against important infections with a reduction in the number of injections, which young children need to endure. However, prelicensure studies of the MMRV revealed that it promoted higher rates of fever and measles-like rash in the 1 to 2 weeks after vaccination vs separate MMR and varicella vaccines.
There has also been evidence that the combined MMRV vaccine may promote a higher risk for seizures vs the separate MMR and varicella vaccines. The current study analyzes data from the VSD to address this issue.
Friday, July 9, 2010
Herpes Zoster in Healthy Infants and Toddlers after Perinatal Exposure To Varicella-Zoster Virus: A Case Series and Review of the Literature
From The Pediatric Infectious Disease Journal®
Xavier Rodríguez-Fanjul, MD; Antoni Noguera, MD, PhD; Asunción Vicente, MD; Maria Antònia González-Enseñat, MD; Rafael Jiménez, MD, PhD; Clàudia Fortuny, MD, PhD*
Abstract
Exposure to varicella-zoster virus in utero or during the first months of life is the main risk factor for the development of herpes zoster (HZ) in healthy children. We report a case series of 16 infants and toddlers who presented with HZ after early exposure to varicella-zoster virus. Two patients had recurrences. Despite the severity of the rash in some cases, the benign course and the long-term good prognosis of HZ in healthy children is noteworthy.
Introduction
Herpes zoster (HZ), also named shingles, is caused by the reactivation of latent varicella-zoster virus (VZV) infection within dorsal root and cranial nerve ganglia. While chickenpox usually occurs in the first years of life, HZ is uncommon in childhood and its incidence increases with age and with other causes of decreased cellular immunity.[1] Children infected with VZV in utero or before one year of age have an increased risk of developing HZ.[2,3] We report a case series of 16 previously healthy children who developed HZ after exposure to VZV during gestation or early infancy and who were referred to and followed up in a tertiary-care pediatric hospital in Barcelona (Spain) from 1993 to 2008.
Discussion
HZ is uncommon among children. In classic studies, its incidence in the pediatric age ranged from 0.2 to 0.74 cases per 1000 person-years.[2,3] A large population-based study from Iceland in the early 90s reported a higher incidence rate, up to 1.6 cases per 1000 person-years.[4] It is possible that the disease occurs more frequently than it is thought in children, but remains under reported because of its benign course, as many patients would not seek medical care.
In the largest published case series of HZ in children to date, only 10% of the patients were apparently healthy at inclusion.[5] Because that study was organized around a hospital-based surveillance system, the inclusion criteria probably biased these results. Despite this, and in the absence of updated population-based studies, most experts agree that HZ is more common among immunocompromised children,[1,3,6,7] especially in patients affected with acute leukemia.[8]
Among healthy children, primary VZV infection during gestation or the first year of life is the major risk factor for childhood onset HZ (incidence rate: 4.1 cases per 1000 person-years).[2,3] In our series, VZV primary infection had occurred in most patients by the age of 4 months. At this early age, the infant is protected by transplacentally transferred maternal VZV-specific antibodies[9] but is unable to develop adequate cellular and humoral immunity to VZV.[10,11] Not surprisingly, the age at onset of HZ has been reported to be lower after early primary VZV infection,[7] reflecting the blunting of VZV-specific immune memory in these patients. The median age at onset of HZ in our series was 22 months, clearly lower than the mean age in other large series of pediatric HZ.[3–5,7]
The diagnosis of HZ is based on clinical judgment.[12] Several sensitive microbiologic methods performed on blister fluid/scrapings are available in case of doubt, including viral cultures, polymerase chain reaction, and direct fluorescent antibody testing. Rashes that may resemble HZ are contact dermatitis, herpes simplex skin infection, and staphylococcal impetigo.[12] HZ in healthy children is mildly symptomatic and usually shows a benign and self-limited course in 1 to 3 weeks; its more common complications are bacterial secondary infection, depigmentation, and scarring. Thoracic dermatomes are involved in 65% to 75% of cases.[3,4] Ocular involvement, which is very frequent in the adult patient, must be always ruled out when the ophthalmic branch of the trigeminal nerve (V1) is affected.[13] Disseminated cutaneous HZ, neurologic complications, visceral dissemination, post-HZ neuralgia, and other sequelae have been very rarely reported in immunocompetent children.[5,7,14] Two of the patients in our series had a second episode of HZ in the same dermatome, which recovered uneventfully. Recurrences have not been previously reported in early childhood HZ and are also infrequent in the immunocompetent adult patient. Junker and Tilley[15] hypothesized that a failure to maintain or evoke a secondary VZV-specific immune response could explain recurrent chickenpox in a series of 23 healthy and apparently immunocompetent children.
Antiviral therapy and hospital admission are rarely needed.[4] In fact, acyclovir in the healthy child is only recommended when ophthalmic HZ or moderate-to-severe symptomatic rash occur; analgesics and appropriate skin care are more often required. In our series, a referral bias probably explains both the predominance of cranial nerve dermatome involvement and the high rates of hospital admission and acyclovir treatment. Despite the severity of the cases we report, a benign course and lack of sequelae ensued in all cases, reflecting the excellent prognosis of pediatric HZ.[4]
Although HIV infection and pediatric malignancies are commonly associated with HZ, childhood HZ has not been found to be the harbinger of an underlying immunodeficiency or malignancy.[4] Because of this, an immunologic work-up should not be routinely performed in previously healthy children affected with a first episode of HZ and would only be justified when recurrences occur.[6]
Finally, several cases of mild and uncomplicated HZ caused by the Oka vaccine strain of VZV have been reported, 65% of them in children <5 years of age.[16]
The incidence of HZ in children is higher after natural varicella infection than after varicella vaccination, in healthy and immunocompromised children.[17] Currently, varicella immunization with the Oka attenuated VZV strain is not publicly funded in Catalonia, despite the recommendation by the Asociación Española de Pediatría.[18] Universal vaccination programs will probably impact HZ epidemiology in the future, as has happened with varicella.[19]
Xavier Rodríguez-Fanjul, MD; Antoni Noguera, MD, PhD; Asunción Vicente, MD; Maria Antònia González-Enseñat, MD; Rafael Jiménez, MD, PhD; Clàudia Fortuny, MD, PhD*
Abstract
Exposure to varicella-zoster virus in utero or during the first months of life is the main risk factor for the development of herpes zoster (HZ) in healthy children. We report a case series of 16 infants and toddlers who presented with HZ after early exposure to varicella-zoster virus. Two patients had recurrences. Despite the severity of the rash in some cases, the benign course and the long-term good prognosis of HZ in healthy children is noteworthy.
Introduction
Herpes zoster (HZ), also named shingles, is caused by the reactivation of latent varicella-zoster virus (VZV) infection within dorsal root and cranial nerve ganglia. While chickenpox usually occurs in the first years of life, HZ is uncommon in childhood and its incidence increases with age and with other causes of decreased cellular immunity.[1] Children infected with VZV in utero or before one year of age have an increased risk of developing HZ.[2,3] We report a case series of 16 previously healthy children who developed HZ after exposure to VZV during gestation or early infancy and who were referred to and followed up in a tertiary-care pediatric hospital in Barcelona (Spain) from 1993 to 2008.
Discussion
HZ is uncommon among children. In classic studies, its incidence in the pediatric age ranged from 0.2 to 0.74 cases per 1000 person-years.[2,3] A large population-based study from Iceland in the early 90s reported a higher incidence rate, up to 1.6 cases per 1000 person-years.[4] It is possible that the disease occurs more frequently than it is thought in children, but remains under reported because of its benign course, as many patients would not seek medical care.
In the largest published case series of HZ in children to date, only 10% of the patients were apparently healthy at inclusion.[5] Because that study was organized around a hospital-based surveillance system, the inclusion criteria probably biased these results. Despite this, and in the absence of updated population-based studies, most experts agree that HZ is more common among immunocompromised children,[1,3,6,7] especially in patients affected with acute leukemia.[8]
Among healthy children, primary VZV infection during gestation or the first year of life is the major risk factor for childhood onset HZ (incidence rate: 4.1 cases per 1000 person-years).[2,3] In our series, VZV primary infection had occurred in most patients by the age of 4 months. At this early age, the infant is protected by transplacentally transferred maternal VZV-specific antibodies[9] but is unable to develop adequate cellular and humoral immunity to VZV.[10,11] Not surprisingly, the age at onset of HZ has been reported to be lower after early primary VZV infection,[7] reflecting the blunting of VZV-specific immune memory in these patients. The median age at onset of HZ in our series was 22 months, clearly lower than the mean age in other large series of pediatric HZ.[3–5,7]
The diagnosis of HZ is based on clinical judgment.[12] Several sensitive microbiologic methods performed on blister fluid/scrapings are available in case of doubt, including viral cultures, polymerase chain reaction, and direct fluorescent antibody testing. Rashes that may resemble HZ are contact dermatitis, herpes simplex skin infection, and staphylococcal impetigo.[12] HZ in healthy children is mildly symptomatic and usually shows a benign and self-limited course in 1 to 3 weeks; its more common complications are bacterial secondary infection, depigmentation, and scarring. Thoracic dermatomes are involved in 65% to 75% of cases.[3,4] Ocular involvement, which is very frequent in the adult patient, must be always ruled out when the ophthalmic branch of the trigeminal nerve (V1) is affected.[13] Disseminated cutaneous HZ, neurologic complications, visceral dissemination, post-HZ neuralgia, and other sequelae have been very rarely reported in immunocompetent children.[5,7,14] Two of the patients in our series had a second episode of HZ in the same dermatome, which recovered uneventfully. Recurrences have not been previously reported in early childhood HZ and are also infrequent in the immunocompetent adult patient. Junker and Tilley[15] hypothesized that a failure to maintain or evoke a secondary VZV-specific immune response could explain recurrent chickenpox in a series of 23 healthy and apparently immunocompetent children.
Antiviral therapy and hospital admission are rarely needed.[4] In fact, acyclovir in the healthy child is only recommended when ophthalmic HZ or moderate-to-severe symptomatic rash occur; analgesics and appropriate skin care are more often required. In our series, a referral bias probably explains both the predominance of cranial nerve dermatome involvement and the high rates of hospital admission and acyclovir treatment. Despite the severity of the cases we report, a benign course and lack of sequelae ensued in all cases, reflecting the excellent prognosis of pediatric HZ.[4]
Although HIV infection and pediatric malignancies are commonly associated with HZ, childhood HZ has not been found to be the harbinger of an underlying immunodeficiency or malignancy.[4] Because of this, an immunologic work-up should not be routinely performed in previously healthy children affected with a first episode of HZ and would only be justified when recurrences occur.[6]
Finally, several cases of mild and uncomplicated HZ caused by the Oka vaccine strain of VZV have been reported, 65% of them in children <5 years of age.[16]
The incidence of HZ in children is higher after natural varicella infection than after varicella vaccination, in healthy and immunocompromised children.[17] Currently, varicella immunization with the Oka attenuated VZV strain is not publicly funded in Catalonia, despite the recommendation by the Asociación Española de Pediatría.[18] Universal vaccination programs will probably impact HZ epidemiology in the future, as has happened with varicella.[19]
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